Insidious Harm of Medication Diluents as a Contributor to Cumulative Volume and Hyperchloremia: A Prospective, Open-Label, Sequential Period Pilot Study*

Magee, Carolyn; Bastin, Melissa L. Thompson; Laine, Melanie; Bissell, Brittany D; Howington, Gavin T.; Moran, Peter; McCleary, Emily; Owen, G.; Kane, Lauren; Higdon, Emily; Pierce, Cathy; Morris, Peter E.; Flannery, Alexander H.

doi:10.1097/ccm.0000000000003191

Cited by 41 publications

(53 citation statements)

References 21 publications

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“…From our previous study of diluent change in the medical ICU, the average fluid balance in our patients at 72 h was positive 2.4 ± 5.1 l [15]. Based on these data, we calculated a sample size of 104 patients in each group to achieve a ≥ 2-l decrease in fluid balance at 72 h postshock, maintaining an 80% power and an alpha of 0.05.…”

Section: Discussionmentioning

confidence: 99%

Impact of protocolized diuresis for de-resuscitation in the intensive care unit

et al. 2020

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Objective: Administration of diuretics has been shown to assist fluid management and improve clinical outcomes in the critically ill post-shock resolution. Current guidelines have not yet included standardization or guidance for diuretic-based de-resuscitation in critically ill patients. This study aimed to evaluate the impact of a multi-disciplinary protocol for diuresis-guided de-resuscitation in the critically ill. Methods: This was a pre-post single-center pilot study within the medical intensive care unit (ICU) of a large academic medical center. Adult patients admitted to the Medical ICU receiving mechanical ventilation with either (1) clinical signs of volume overload via chest radiography or physical exam or (2) any cumulative fluid balance ≥ 0 mL since hospital admission were eligible for inclusion. Patients received diuresis per clinician discretion for a 2-year period (historical control) followed by a diuresis protocol for 1 year (intervention). Patients within the intervention group were matched in a 1:3 ratio with those from the historical cohort who met the study inclusion and exclusion criteria. Results: A total of 364 patients were included, 91 in the protocol group and 273 receiving standard care. Protocolized diuresis was associated with a significant decrease in 72-h post-shock cumulative fluid balance [median, IQR − 2257 (− 5676-920) mL vs 265 (− 2283-3025) mL; p < 0.0001]. In-hospital mortality in the intervention group was lower compared to the historical group (5.5% vs 16.1%; p = 0.008) and higher ICU-free days (p = 0.03). However, no statistically significant difference was found in ventilator-free days, and increased rates of hypernatremia and hypokalemia were demonstrated. Conclusions: This study showed that a protocol for diuresis for de-resuscitation can significantly improve 72-h post-shock fluid balance with potential benefit on clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

Impact of protocolized diuresis for de-resuscitation in the intensive care unit

et al. 2020

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“…In addition to the passive (restrictive) resuscitation strategies outlined in the prospective studies, the clinician should remain cognizant of the contribution of maintenance fluids and medications to overall daily fluid volume. As much as 24.7% of a daily fluid volume are derived from these sources, and medication diluents can account for up to 63% of total intravenous volume in a general medical ICU population . Combined restriction of diluents, maintenance fluids, and post‐resuscitation volume stewardship can substantially contribute to optimizing a patient’s fluid balance.…”

Section: After the Resuscitation Phase: Passive De‐resuscitationmentioning

confidence: 99%

“…As much as 24.7% of a daily fluid volume 44 are derived from these sources, and medication diluents can account for up to 63% of total intravenous volume in a general medical ICU population. 45 Combined restriction of diluents, maintenance fluids, and post-resuscitation volume stewardship can substantially contribute to optimizing a patient's fluid balance.…”

Section: After the Resuscitation Phase: Passive Deresuscitationmentioning

confidence: 99%

Establishing the Therapeutic Index of Fluid Resuscitation in the Septic Patient: A Narrative Review and Meta‐Analysis

2020

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This comprehensive review comparatively evaluates the safety and benefits of parenteral fluids used in resuscitation with a focus on sepsis. It also provides a random‐effects meta‐analysis of studies comparing restrictive resuscitation and usual care in sepsis with the primary outcome of mortality. In the septic patient, fluid therapy remains a complex interplay between fluid compartments in the body, the integrity of the endothelial barrier, and the inflammatory tone of the patient. Recent data have emerged describing the pharmacokinetics of fluid resuscitation that can be affected by the factors just listed, as well as mean arterial pressure, rate of infusion, volume of fluid infusate, nature of the fluid, and drug interactions. Fluid overload in sepsis has been associated with vasodilation, kidney injury, and increased mortality. Restrictive resuscitation after the initial septic insult is an emerging practice. Our search strategy of Medline databases revealed six randomized studies with 706 patients that examined restrictive resuscitation in sepsis. Results of this meta‐analysis demonstrated no differences in mortality with restrictive resuscitation compared with usual care (30.6% vs 37.8%; risk ratio 0.83, 95% confidence interval 0.66–1.05, respectively) but was limited by the small number of studies and larger quantities of pre‐randomization fluids. Another approach to address fluid overload is active (diuresis) de‐resuscitation strategies that may shorten the need for mechanical ventilation and intensive care unit length of stay. Data suggest that colloids may confer mortality benefit over saline in the most severely ill septic patients. Compared with isotonic saline, balanced resuscitation fluids are associated with a lower incidence of acute kidney injury and mortality. The benefits of balanced resuscitation fluids are most evident when higher volumes of fluids are used for sepsis. Clinicians should consider these pharmacotherapeutic factors when selecting a fluid, its quantity, and rate of infusion.

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“…On the other hand, research focusing on the choice of drug diluents has been limited. We believe that the drug diluents may play an important role because critically ill patients generally require many types of drugs, including antibiotics and sedatives [6,7]. The total amount of diluents administered may be high enough to introduce abnormalities in serum electrolyte and glucose levels.…”

Section: Introductionmentioning

confidence: 99%

Saline versus 5% dextrose in water as a drug diluent for critically ill patients: a retrospective cohort study

et al. 2020

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Background The choice of intravenous infusion products for critically ill patients has been studied extensively because it can affect prognosis. However, there has been little research on drug diluents in this context. The purpose of this study is to evaluate the impact of diluent choice (saline or 5% dextrose in water [D5W]) on electrolyte abnormalities, blood glucose control, incidence of acute kidney injury (AKI), and mortality. Methods This before-after, two-group comparative, retrospective study enrolled adult patients who stayed for more than 48 h in a general intensive care unit from July 2015 to December 2018. We changed the default diluent for intermittent drug sets in our electronic ordering system from D5W to saline at the end of 2016. Results We included 844 patients: 365 in the D5W period and 479 in the saline period. Drug diluents accounted for 21.4% of the total infusion volume. The incidences of hypernatremia and hyperchloremia were significantly greater in the saline group compared to the D5W group (hypernatremia 27.3% vs. 14.6%, p < 0.001; hyperchloremia 36.9 % vs. 20.4%, p < 0.001). Multivariate analyses confirmed the similar effects (hypernatremia adjusted odds ratio (OR), 2.43; 95% confidence interval (CI), 1.54–3.82; hyperchloremia adjusted OR, 2.09; 95% CI, 1.31–3.34). There was no significant difference in the incidences of hyperglycemia, AKI, and mortality between the two groups. Conclusions Changing the diluent default from D5W to saline had no effect on blood glucose control and increased the incidences of hypernatremia and hyperchloremia.

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Insidious Harm of Medication Diluents as a Contributor to Cumulative Volume and Hyperchloremia: A Prospective, Open-Label, Sequential Period Pilot Study*

Abstract: This study identified that medication diluents contribute substantially to the total IV volume received by critically ill patients. Saline as the primary medication diluent compared with dextrose 5% in water is associated with hyperchloremia, a possible risk factor for acute kidney injury.

Cited by 41 publications

References 21 publications

Impact of protocolized diuresis for de-resuscitation in the intensive care unit

Impact of protocolized diuresis for de-resuscitation in the intensive care unit

Establishing the Therapeutic Index of Fluid Resuscitation in the Septic Patient: A Narrative Review and Meta‐Analysis

Saline versus 5% dextrose in water as a drug diluent for critically ill patients: a retrospective cohort study

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