# Discarded intravenous medication in the ICU: the GAME-OVER multicenter prospective observational study

Erwan D'aranda, Stéphanie Pons, Jonathan Chelly, Enora Atchade, Laure Bonnet, Claire Dahyot-Fizelier, Toufik Kamel, Fanny Giannoni, Olivier Collange, Emmanuel Besnier, et al.

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## To cite this version:

Erwan D'aranda, Stéphanie Pons, Jonathan Chelly, Enora Atchade, Laure Bonnet, et al. Discarded intravenous medication in the ICU: the GAME-OVER multicenter prospective observational study. Critical Care, 2025, 29 (1), pp.84. 10.1186/s13054-025-05299-6. hal-05073581

HAL Id: hal-05073581

https://hal.science/hal-05073581v1

Submitted on 19 May 2025

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# Discarded intravenous medication in the ICU: the GAME-OVER multicenter prospective observational study

Erwan d'Aranda¹,²,⁰*, Stéphanie Pons²,³, Jonathan Chelly⁴,⁵, Enora Atchade⁶, Laure Bonnet⁷, for the SFAR Sustainable Development Committee, Claire Dahyot-Fizelier⁸, for the SFAR Critical Care Committee, Toufik Kamel⁹, Fanny Giannoni¹, Olivier Collange¹⁰, Emmanuel Besnier¹¹, Mathieu Schoeffler¹², Nicolas Mayeur¹³, Pierre-Louis Quere¹, Ludivine Marecal¹⁴,¹⁵, Cyril Pernod¹⁶,¹⁷, Cyrille Geay¹, Pierre Esnault¹, Raphaël Cinotti¹⁸,¹⁹, for the SFAR Research Network, Magali Cesana⁵ and Pierre-Julien Cungi¹

**Abstract**

**Background** Medication waste is a contributor to the healthcare environmental footprint and impacts ecosystems. Data on medication waste in the intensive care unit (ICU) are scarce, and therefore are essential to develop new sustainable strategies.

**Methods** The GAME-OVER French multicenter prospective observational study was conducted from November 2022 to March 2023, over a 24-h period of choice, at the discretion of each participating center. Adult ICUs were enrolled in the study on a voluntary basis and hospitalized patients who did not express opposition were included in the analysis. The primary endpoint was the percentage of discarded intravenous (IV) medication in the ICU, defined as the ratio of the discarded volume to the total volume of IV medication prepared. Secondary endpoints included identifying risk factors and main reasons for medication waste and estimating its related healthcare cost.

**Results** Among the 81 ICUs and the 1076 enrolled patients, 408.9 L of 130 IV medications were prepared. The discarded volume was 43.8 L, resulting in a 10.7% discarded IV medication (95% Confidence Interval (CI), 9.9–11.5). Number of daily admissions/discharges in the ICU, as admission for elective surgery, Sequential Organ Failure Assessment score ≥ 7, endotracheal intubation, renal replacement therapy and body mass index were independently associated with increased discarded IV medication. Ninety percent of pharmaceutical waste was attributed to 25 key drugs, with an estimated national annual cost of 2,737,163€.

**Conclusions** Discarded intravenous medication in the ICU is considerable and results in significant costs for the health care system, without obvious patient-centered value. Risk factors associated with medication waste were largely nonmodifiable, emphasizing the need for sustainable practices in patient care and resource management.

**Trial Registration** ClinicalTrials.gov: NCT05553054. September 23, 2022.

**Keywords** Sustainable healthcare, Ecodesign of healthcare, Pharmaceutical waste, Drug waste, Healthcare cost, Environment

<footnote>*Correspondence:
Erwan d'Aranda
erwan.daranda@gmail.com
Full list of author information is available at the end of the article</footnote>
## Graphical Abstract

# The GAME – OVER study

### A national multicenter prospective observational study in 81 French adult ICUs

* **Primary Objective:** Evaluate the percentage of discarded intravenous medication (DIVM) over a 24-hour period

* **Secondary Objectives:** Identify risk factors associated with increased discarded IV medication
  Evaluate its healthcare cost

**Population: 81 ICUs - 1076 patients**

Age - mean (SD) 59.6 (16.5)

Female n=377 (36%)

Body mass index - mean (SD) 26.9 (7.07)

SOFA score - median (IQR) 4.00 (2-7)

Invasive mechanical ventilation n= 490 (45.5%)

**Discarded intravenous medication volume =**
10.7% (95% CI 9.9 - 11.5)

408.9 L prepared

43.8 L discarded

**Multivariate analysis of risk factors associated with increased DIVM**

Elective surgery OR = 1.81 [1.24-2.64]

SOFA score ≥ 7 OR = 1.56 [1.12-2.19]

Endotracheal intubation OR = 2.14 [1.57-2.92]

Renal replacement therapy OR = 1.62 [1.06-2.50]

Body mass index OR = 1.02 [1.00-1.04]

<figure><img src="image_4.png" /></figure>

Annual estimated cost of the
25 most wasted intravenous
medications in French ICUs
2,737,163 €

## Introduction

Worldwide, healthcare systems are playing an active role in greenhouse gases (GHG) production as well as in water, air, and soil pollution [1–4]. Climate change is increasingly impacting human health, requiring healthcare professionals to assess their practices, take responsibility, and implement strategies to reduce their environmental footprint [5–8].

Pharmaceuticals represent an important share of healthcare GHG emissions [9, 10]. Medication supply chain directly induces loss of natural resources and participates in global warming [11]. Medication waste, aside to its unnecessary cost, has been shown to significantly impact the environment [12, 13]. Pharmaceutical residues, by contaminating wastewater, contribute to aquatic environment pollution and disrupt ecosystems [14]. Improper antimicrobial waste disposal also significantly influences antibiotic resistance, resulting in potential life-threatening consequences on human health [15].

Implementing new practices, and adjusting containers volume and size are known to reduce pharmaceutical waste and costs [16, 17]. In the intensive care unit (ICU), critical care pharmacist interventions enhance quality of care while decreasing pharmaceutical consumption and costs [18, 19]. Thus, medication waste

can be limited by integrating the ecodesign of healthcare concept in our daily clinical practice, without altering safety nor quality of care. Preventing and minimizing pharmaceutical waste could then help to reduce the environmental impact of healthcare while decreasing associated costs.

However, to address this issue and implement sustainable practices, medication waste assessment in various healthcare settings is essential. Pharmaceutical waste data in the ICU are scarce. Few studies have investigated discarded intravenous medication (DIVM) in the ICU, and primarily focusing on antimicrobials waste and its sustainability impact [20, 21]. Other data arise from anesthesia and the operating theater (OT), where intravenous (IV) medications preparation and administration share some similarities with the ICU [10, 22]. However, ICU activity displays very specific features compared to the OT, notably a longer length of stay; a decreased patient turnover; continuous care and monitoring for a higher number of patients, which can directly impact DIVM.

The aim of our study was to assess DIVM in the ICU, and to identify areas for improvement in our daily practices to limit any avoidable wastage and reduce healthcare costs.
# Methods

## Study design and oversight

We conducted a one-day French multicenter prospective observational study in adult ICUs. The protocol was approved by an institutional review board (IRB) on September 15, 2022 (Centre Hospitalier Intercommunal de Toulon-La Seyne-sur-Mer, France, IRB 12962) and registered in the clinicaltrials.gov database (NCT05553054). Inclusions and data collection were performed during one working day in each ICU, anytime between November 08, 2022, and March 06, 2023, at the discretion of each participating team. Demographical and clinical data were collected at inclusion. The study did not involve clinical follow-up. The database was approved by all the participating centers and by the sponsor's Data Protection Officer, in accordance with the European Union general data protection regulation. The «Strengthening the Reporting of Observational studies in Epidemiology» (STROBE) statement checklist, the protocol, and the statistical report containing source code are available in Additional files 1, 2 and 3, respectively. The Centre Hospitalier Intercommunal de Toulon-La Seyne-sur-Mer funded and sponsored the study.

## Participating ICUs and patients

All the participating centers were recruited through the French Society of Anesthesia & Intensive Care Medicine (SFAR) Research Network, the Sustainability Committee and the Critical Care Committee. University hospitals, tertiary centers, and private hospitals with ICU beds were eligible to participate. Intermediate care units were excluded from the study. In accordance with French law, all the adult patients hospitalized in the participating ICU on inclusion day, or their next of kin if the patients were unable to provide consent, were informed of the study protocol and included unless they explicitly objected to data collection.

## Data collection

Data were collected over a 24-h period in each ICU. The characteristics of the participating ICUs were recorded, as well as clinical and demographical data of the enrolled patients. A full list of the data recorded is available in the protocol and in the Additional file 1. For each patient, throughout the day of the study, all the IV medication containers (syringes, bottles, fluid bags) from continuous or bolus infusions were discarded in a personal waste container. All the medications either prepared directly in the ICU or compounded by the central pharmacy were collected and included in the analysis. If residual volume (defined as a volume greater than 2 mL) was present in the discarded container, reason for disposal was reported by the attending nurse, as follows: prepared

medication remained unused, systematic change at a predefined time, prescription modification, forward-planned changes, no longer required medication due to clinical evolution, medication preparation error, or other. Forward-planned changes were defined as changes made by the attending nurse earlier than prescribed to accommodate other duties. When DIVM were not assigned to a specific patient, they were collected in a container shared for all the ICU. Whether at the end of the study day, or at patient discharge, the investigator reported the contents of the containers: medication names, dilution of the DIVM (in mg/mL or International Units/mL) and container types and volume (syringes/bags). The number of discarded containers, the number of containers containing unused medication, the number of containers discarded while full (defined by a volume greater than 90% of the total prepared volume), as well as the initial volume prepared and the residual discarded volume for each container were also collected. Preparation and administration of IV medications were performed by the nursing staff. Primary vials (containing freeze dried-powder or liquid), used to reconstitute medication solutions, as well as their residual volume/medication, were not included in waste analysis. The medication volume, obtained after dilution from the primary vial, was collected for each IV medication container. Electrolyte solutions, crystalloids, colloids, and blood products were excluded from DIVM. Additionally, a survey regarding medication preparation and pharmaceutical waste management by the attending nurses was simultaneously conducted in each participating center. Additional methods are provided in Additional file 1.

## Outcomes

The primary endpoint was the percentage of DIVM, defined as the ratio of the discarded volume to the total volume of medications prepared. Key secondary endpoints included the identification of causes and risk factors associated with DIVM, and the evaluation of healthcare costs related to DIVM.

## Statistical analyses

Quantitative variables are reported as median and interquartile range, or mean ± standard deviation, depending on the normality of their distribution, which was tested by a Shapiro-Wilk normality test. Categorical variables are reported as numbers (percentages). The primary endpoint is reported as percentage and 95% confidence interval (95% CI) established by the bootstrap resampling method, using 1000 iterations (R package boot V1.3-28.1). Quantitative variables were compared using Student's *t* test, or Wilcoxon-Mann-Whitney test, as appropriate. Categorical variables
were compared using semi-parametric Chi-square. Yates correction was used if expected frequency was under 5. To identify associated risk factors for DIVM, ICUs as well as patients were each divided into two groups ("low DIVM" and "high DIVM") by the median DIVM threshold. Multivariate analyses were performed using a backward stepwise logistic regression model after selecting variables with a *p*-value < 0.2 in univariate analysis. Odds ratio (OR) are expressed with their 95% CI. The validity of the model was tested by a Hosmer–Lemeshow test. The optimal categorization of the continuous variable into separate categories was obtained with the CatPredi model as previously described by Barrio et al.[23]. To estimate DIVM cost, we excluded medical devices and preparation time, and we averaged the prices of the 25 most discarded drugs from three different participating centers and extrapolated the healthcare cost per year using the number of ICU hospitalization days in France in 2022, obtained from the French national medico-economic hospital database [24]. Statistical analyses were performed by the last author using R statistics (CRAN), version 4.1.1.

# Results

## Study population and ICUs characteristics

Eighty-one French ICUs were enrolled in the study, including 1218 ICU beds. Data on DIVM were recorded in 1076 patients. Clinical data were analyzed for 1048 patient, as 28 patients (2.6%) did not consent to data collection. The survey was completed by 823 out of the 988 nurses (83%) who were working during the study-day. General characteristics regarding ICUs and the overall cohort are provided in Tables 1 and 2, respectively. Participating ICUs were mainly mixed (56%), and surgical (36%). Overall, 348 patients (33.3%) were under continuous sedation, and 507 (48.4%) had an endotracheal tube. The median number of admissions and/or discharges per ICU was 4 (IQR, 1–6).

## Primary endpoint

In total, 408.9 L (liters) of 130 medications were prepared in all participating ICUs. The median discarded volume per ICU was 477 mL (IQR, 235–729 mL) (eFigure 1). Overall, 6519 containers were collected, representing a median of 6 (IQR, 3–10) containers per patient per day (eFigure 2). The total discarded volume of IV medication was 43.8 L, resulting in a 10.7% DIVM (95% CI, 9.9–11.5). Residual volume greater than 2 mL was found in 2007

<table><caption>**Table 1** ICUs characteristics, in the overall cohort, and in the "low DIVM" and "high DIVM" ICU groups</caption><thead><tr><th>ICU characteristics</th><th>Overall ICUs (N=81)</th><th>Low DIVM ICU (N=40)</th><th>High DIVM ICU (N=41)</th><th>p</th></tr></thead><tbody><tr><td>Hospital type—n (%)</td><td></td><td></td><td></td><td>0.16</td></tr><tr><td>University hospital</td><td>44 (54)</td><td>18 (45)</td><td>26 (63)</td><td></td></tr><tr><td>Public hospital</td><td>25 (31)</td><td>13 (33)</td><td>12 (29)</td><td></td></tr><tr><td>Private hospital</td><td>7 (9)</td><td>6 (15)</td><td>1 (2)</td><td></td></tr><tr><td>Military teaching hospital</td><td>5 (6)</td><td>3 (8)</td><td>2 (5)</td><td></td></tr><tr><td>ICU main activity—no. (%)</td><td></td><td></td><td></td><td>0.79</td></tr><tr><td>Mixed</td><td>45 (56)</td><td>24 (60)</td><td>21 (51)</td><td></td></tr><tr><td>Surgical</td><td>29 (36)</td><td>12 (30)</td><td>17 (42)</td><td></td></tr><tr><td>Medical</td><td>5 (6)</td><td>3 (8)</td><td>2 (5)</td><td></td></tr><tr><td>Burn patients</td><td>2 (3)</td><td>1 (3)</td><td>1 (2)</td><td></td></tr><tr><td>Available beds per ICU—median (IQR)</td><td>13 (10–16)</td><td>12 (10–16)</td><td>15 (12–17)</td><td>0.07</td></tr><tr><td>Patients hospitalized per ICU—median (IQR)</td><td>12 (9–15)</td><td>10.5 (8–13)</td><td>13 (10–17)</td><td>0.03*</td></tr><tr><td>Admissions and/or discharges—median (IQR)</td><td>4 (1–6)</td><td>2 (1–4)</td><td>4 (3–6)</td><td>&lt; 0.01*</td></tr><tr><td>Bed-to-nurse ratio (day)—median (IQR)</td><td>2.4 (2.0–2.7)</td><td>2.4 (2–2.7)</td><td>2.4 (1.9–2.5)</td><td>0.45</td></tr><tr><td>Bed-to-nurse ratio (night)—median (IQR)</td><td>2.7 (2.4–3.0)</td><td>2.7 (2.5–3.0)</td><td>2.5 (2.1–3.0)</td><td>0.11</td></tr><tr><td>Bed-to-intensivist ratio (day)—median (IQR)</td><td>5.0 (4.0–6.7)</td><td>5.0 (4.0–6.8)</td><td>5.0 (4.0–6.7)</td><td>0.40</td></tr><tr><td>Presence of student nurses—no. (%)</td><td>44 (55)</td><td>19 (48)</td><td>25 (63)</td><td>0.26</td></tr><tr><td>Presence of residents—no. (%)</td><td>77 (95)</td><td>36 (90)</td><td>41 (100)</td><td>0.06</td></tr><tr><td>Median % of DIVM (IQR)</td><td>9 (6–16)</td><td>6 (3–8)</td><td>16 (11–26)</td><td>&lt; 0.001*</td></tr></tbody></table>

Univariate analyses of ICUs characteristics were performed between the two groups, divided by the median DIVM. The "low DIVM ICU" group was defined as the first and second quartiles and the "high DIVM ICU" group was defined as the third and fourth quartiles. Median DIVM was calculated for 1076 patients hospitalized in the 81 enrolled ICUs. *p* < 0.05* was considered statistically significant

ICU, Intensive Care Unit; IQR, Interquartile Range; DIVM, Discarded IntraVenous Medication
<table><caption>**Table 2** Population characteristics, in the overall cohort, and in the "low DIVM" and "high DIVM" patients' groups</caption><thead><tr><th>Population characteristics</th><th>Overall cohort (N = 1048)</th><th>Low DIVM patients (N = 519)</th><th>High DIVM patients (N = 529)</th><th>p</th></tr></thead><tbody><tr><td>Age, yr—mean (SD)</td><td>59.6 (16.5)</td><td>58.9 (16.7)</td><td>60.3 (16.4)</td><td>0.18</td></tr><tr><td>Sex female—no. (%)</td><td>377 (36)</td><td>187 (36)</td><td>190 (36)</td><td>1.0</td></tr><tr><td>Body mass index (kg/m²)—mean (SD)</td><td>26.9 (7.07)</td><td>26.5 (6.6)</td><td>27.4 (7.4)</td><td>0.04*</td></tr><tr><td>Indication for ICU admission—no. (%)</td><td></td><td></td><td></td><td>0.04*</td></tr><tr><td>Elective surgery</td><td>165 (15.8)</td><td>67 (13)</td><td>98 (18.6)</td><td></td></tr><tr><td>Emergency surgery</td><td>246 (23.6)</td><td>133 (25.8)</td><td>113 (21.4)</td><td></td></tr><tr><td>Medical</td><td>546 (52.3)</td><td>277 (53.7)</td><td>269 (50.9)</td><td></td></tr><tr><td>Traumatology</td><td>87 (8.33)</td><td>39 (7.6)</td><td>48 (9.1)</td><td></td></tr><tr><td>SOFA score—median (IQR)</td><td>4 (2–7)</td><td>3 (1–6)</td><td>5 (2–8)</td><td>&lt;0.001*</td></tr><tr><td>Continuous sedation—no. (%)</td><td>348 (33.2)</td><td>122 (23.6)</td><td>226 (42.7)</td><td>&lt;0.001*</td></tr><tr><td>Upper airway access—no. (%)</td><td></td><td></td><td></td><td>&lt;0.001*</td></tr><tr><td>None</td><td>540 (51.6)</td><td>318 (61.4)</td><td>222 (42.0)</td><td></td></tr><tr><td>Endotracheal intubation</td><td>443 (42.3)</td><td>161 (31.1)</td><td>282 (53.3)</td><td></td></tr><tr><td>Tracheostomy</td><td>64 (6.1)</td><td>39 (7.5)</td><td>25 (4.7)</td><td></td></tr><tr><td>Oxygen therapy—no. (%)</td><td></td><td></td><td></td><td>&lt;0.001*</td></tr><tr><td>None</td><td>215 (20.0)</td><td>146 (27.1)</td><td>69 (12.8)</td><td></td></tr><tr><td>Invasive mechanical ventilation</td><td>490 (45.5)</td><td>187 (34.8)</td><td>303 (56.3)</td><td></td></tr><tr><td>Non-invasive ventilation</td><td>70 (6.5)</td><td>35 (6.5)</td><td>35 (6.5)</td><td></td></tr><tr><td>High-flow nasal cannula oxygen therapy</td><td>57 (5.3)</td><td>33 (6.1)</td><td>24 (4.5)</td><td></td></tr><tr><td>Standard oxygen therapy</td><td>244 (22.7)</td><td>137 (25.5)</td><td>107 (19.9)</td><td></td></tr><tr><td>Renal replacement therapy—no. (%)</td><td>125 (12.0)</td><td>45 (8.7)</td><td>80 (15.2)</td><td>&lt;0.01*</td></tr><tr><td>Enteral route available—no. (%)</td><td>873 (83.3)</td><td>442 (85.7)</td><td>431 (81.5)</td><td>0.08</td></tr><tr><td>Patient discharges on D-day—no. (%)</td><td>141 (13.5)</td><td>79 (15.3)</td><td>62 (11.7)</td><td>0.11</td></tr><tr><td>Number of ICU days—median (IQR)</td><td>5 (1–14)</td><td>6 (2–16)</td><td>4 (1–11)</td><td>&lt;0.01*</td></tr><tr><td>ICU length of stay &lt; 48 h—no. (%)</td><td>367 (35.0)</td><td>166 (32.2)</td><td>201 (38.2)</td><td>0.05</td></tr><tr><td>Median % of DIVM (IQR)</td><td>4 (0–18)</td><td>0 (0–0.8)</td><td>18 (9–36)</td><td>&lt;0.001*</td></tr></tbody></table>

Univariate analyses of the population characteristics were performed between the two groups, divided by the median DIVM. The "low DIVM patients" group was defined as the first and second quartiles and the "high DIVM patients" group was defined as the third and fourth quartiles. Median DIVM was calculated for 1076 patients hospitalized in the 81 enrolled ICUs. Demographical and clinical data were available in 1048 patients. *p* < 0.05* was considered statistically significant

ICU, Intensive Care Unit; IQR, Interquartile Range; DIVM, Discarded IntraVenous Medication; SD, Standard deviation; SOFA score, Sequential Organ Failure Assessment score

containers (30.8%). Moreover, 429 (6.5%) containers were considered full when being thrown away, representing a volume of 21.0 L and 5.1% of the total prepared medication volume.

## Risk factors associated with increased discarded intravenous medication

To identify risk factors for pharmaceutical waste, both ICUs and patients were split in two groups by the median DIVM, which was 9.1% (IQR, 6.1–16.3) for the overall ICUs and 3.8% (IQR, 0.0–17.8) for the cohort of patients. Multivariate analysis on ICU characteristics showed that the number of admissions/discharges was the only factor significantly associated with increased DIVM (OR 1.27; 95% CI, 1.08 to 1.55; *p* < 0.01, Hosmer–Lemeshow test *p* = 0.54). When focusing on patient characteristics, multivariate analysis showed that ICU admission for elective

surgery (OR 1.81; 95% CI, 1.24–2.64; *p* = 0.02), SOFA score ≥ 7 (OR 1.56; 95% CI 1.12–2.19; *p* < 0.01), endotracheal intubation (OR 2.14; 95% CI, 1.57–2.92; *p* < 0.001), renal replacement therapy (RRT) (OR 1.62; 95% CI, 1.06–2.50, *p* = 0.03), and body mass index (OR 1.02; 95% CI, 1.0–1.04), were significantly associated with increased DIVM (Fig. 1). Risk factors associated with the number of discarded containers are presented in the supplemental results section of Additional file 1.

## Reasons for intravenous medication waste

Of the 2007 discarded containers with residual pharmaceuticals, attending nurses provided explanations for the presence of leftover medications in 1788 cases (89%) (eFigure 3). Prescription modification (n = 477/1788, 27%) and medications no longer required (n = 352/1788, 20%) were the main reasons for discarding a container
<table><caption>**Fig. 1** Multivariate analysis of patients-related risk factors for discarded intravenous medication. An Odds Ratio greater than 1.0 indicates an association with increased discarded intravenous medication. Multivariate analysis was performed using a backward stepwise logistic regression model after selecting variables with a *p*-value < 0.2 in univariate analysis: age, body mass index, indication for intensive care unit (ICU) admission, total Sequential Organ Failure Assessment (SOFA) score, continuous sedation, upper airway access, oxygen therapy, renal replacement therapy, enteral route available, patient discharges on the study day, ICU length of stay. The optimal categorization of the SOFA score, a continuous variable into separate categories was obtained with the CatPredi model (Hosmer–Lemeshow test *p* = 0.18). A *p* value < 0.05 was considered significant</caption><thead><tr><th>Variable</th><th></th><th>N</th><th>Odds ratio</th><th>p</th></tr></thead><tbody><tr><td rowspan="4">Admission Indication</td><td>Medical</td><td>525</td><td>Reference</td><td></td></tr><tr><td>Elective surgery</td><td>160</td><td>1.81 (1.24, 2.64)</td><td>0.002</td></tr><tr><td>Emergency surgery</td><td>231</td><td>0.92 (0.66, 1.27)</td><td>0.599</td></tr><tr><td>Traumatology</td><td>85</td><td>1.34 (0.83, 2.18)</td><td>0.232</td></tr><tr><td rowspan="2">SOFA Score</td><td>[0,6]</td><td>701</td><td>Reference</td><td></td></tr><tr><td>[7,22]</td><td>300</td><td>1.56 (1.12, 2.19)</td><td>0.009</td></tr><tr><td rowspan="3">Upper Airway Access</td><td>None</td><td>513</td><td>Reference</td><td></td></tr><tr><td>Endotracheal intubation</td><td>425</td><td>2.14 (1.57, 2.92)</td><td>&lt;0.001</td></tr><tr><td>Tracheostomy</td><td>63</td><td>0.90 (0.52, 1.56)</td><td>0.720</td></tr><tr><td rowspan="2">Renal replacement therapy</td><td>No</td><td>883</td><td>Reference</td><td></td></tr><tr><td>Yes</td><td>118</td><td>1.62 (1.06, 2.50)</td><td>0.029</td></tr><tr><td>Body Mass Index</td><td></td><td>1001</td><td>1.02 (1.00, 1.04)</td><td>0.035</td></tr><tr><td rowspan="2">Enteral route available</td><td>Yes</td><td>839</td><td>Reference</td><td></td></tr><tr><td>No</td><td>162</td><td>1.34 (0.93, 1.92)</td><td>0.114</td></tr></tbody></table>

with residual volume. Interestingly, 10% of the containers (n=182) were discarded because the medications were prepared in advance to provide care and remained unused. In the survey, 504 out of 823 nurses (61%) acknowledged that they sometimes prepared medications which were not prescribed, and 166 (20%) indicated that they systematically changed all the syringes at a pre-defined time of the day.

## Wasted pharmaceuticals and associated healthcare costs

Excluding electrolytes, crystalloids, and colloids, over 90% of the total discarded volume was represented by 25 intravenous medications. Epinephrine had the highest waste ratio with 68% of the prepared volume remained unused (or the prepared drug quantity), followed by norepinephrine (30%) and dobutamine (30%) (eTable 1). The total discarded volume of norepinephrine was 10.1 L, representing 26% of the disposed volume of the 25 most DIVM, followed by propofol (15%) and insulin (10%) (Fig. 2). However, even though heparin accounted for only 7% of the DIVM volume, it was associated with the highest waste cost (13% of the total estimated cost). Dexmedetomidine, and propofol also represented an

important share of the DIVM costs (Fig. 2). Finally, the daily median cost of the 25 most discarded medications per ICU was 15.9€ (IQR, 8.2–30.7) (eFigure 4), and the total daily cost of DIVM was estimated at 1760€ for the 81 ICUs (eTable 1), representing 1.64€ per patient per ICU-day. Considering that 1,673,402 ICU days were recorded in France in 2022 [24], the national total DIVM in ICU was estimated at 68,118 L. Focusing on the 25 most discarded IV medications, the national DIVM in ICU was evaluated at 60,552 L, representing a healthcare cost of 2,737,163€ annually.

## Discussion

In the GAME-OVER French multicenter prospective ICU study, we reported that DIVM accounted for more than 10% of the total volume of medications prepared. Over one third of the containers were discarded with residual medication and 6.5% were thrown away while being full. We also showed in multivariate analyses that the daily number of admissions and/or discharges per ICU, as well as ICU admission for elective surgery or patients severity factors (SOFA score ≥ 7, RRT or endotracheal intubation) were significantly associated with DIVM. Finally,
<figure><img src="image_5.png" /><figcaption>**Fig. 2** The 25 most discarded medications in the overall cohort. The percentage of volume disposed (orange bars) represents the ratio of the volume disposed of the molecule to the total discarded volume of the 25 most discarded medications. The average price of each medication per milligram (or international unit (IU) for insulin and heparin) was calculated using prices obtained from 3 different hospitals. Solvents, medical devices, and preparation time were excluded from the estimated cost. The percentage of waste cost (blue bars) represents the price of the amount of mg (or IU) thrown away per molecule to the total cost of the 25 most discarded medications</figcaption></figure>

we extrapolated that, in addition to its environmental impact, DIVM in the ICU represented over 2,500,000€ annual healthcare costs in France.

Interestingly, the percentage of DIVM in the ICU was lower than what we expected, considering that a medication waste rate over 30% has been reported in the OT [13, 22, 25, 26]. This could be explained first by the exclusion of electrolytes and vials in our study, as well as differences in daily practice. In our study, the six medications contributing the most to DIVM were norepinephrine, propofol, insulin, heparin, sufentanil, and midazolam, which can be easily explained by the frequent use of continuous sedation, vasopressors, or anticoagulation in critically ill patients. These discarded medications, although daily used in the OT, are partially different from those identified in anesthesia [22, 27], mostly represented by epinephrine, atropine, and phenylephrine. Nevertheless, propofol, which is known for its significant impact on aquatic ecosystems, is highly wasted in both settings [22, 25, 26, 28].

We identified several risk factors associated with increased DIVM. Multiple patient severity criteria (SOFA score ≥ 7, endotracheal intubation and RRT) were significantly associated with DIVM. Patients with multiorgan failure often require continuous sedation, both factors

being also significantly associated with an increased number of discarded containers. Although intermediate care units were excluded from the GAME-OVER study, the population median SOFA score was quite low (4 (IQR 2–7)), which could partially explain the limited DIVM in our study (10.7% (95% CI, 9.9–11.5)). Interestingly, postoperative admission for elective surgery was also identified as a risk factor for waste. Early sedation interruption or IV medication changes after ICU admission could partly explain this association. Moreover, in patients requiring renal replacement therapy, dosage adjustment (i.e. antimicrobials) might also lead to more DIVM although not studied in the literature. However, patient-related risk factors do not allow development of targeted strategies to reduce DIVM. Our results therefore emphasize the need for implementing sustainable practices in daily patient care. Thus, medications with a waste rate over 25% (epinephrine, norepinephrine, dobutamine) could benefit from several specific actions: decreasing the volume of medication prepared in advance, using smaller containers, or using prefilled syringes. Prefilled syringes containing emergency medications, although produced at a higher unit cost than conventional preparations, reduce overall costs by cutting down on wastage while reducing medication administration errors [29, 30].
Clinical pharmacist presence in the ICU, while not being
routine in France, could also help decrease DIVM [19,
30].

In this study, prescription modification was reported as
the main reason for disposing of containers with residual
volume, highlighting the importance of communication
between prescribers and nurses to optimize medications
preparation and decrease associated waste. Optimizing
medication prescription also contributes to the ecodesign
of healthcare and can significantly reduce the environ-
mental impact of pharmaceuticals by applying the prin-
ciple of “right prescription”: the right patient—the right
medication—the right route—the right time—the right
dose—and now the right environmental impact [31].
Finally, raising awareness on our practices is essential.
Systematic syringe changes at a predefined time of the
day, although not supported by any national policy, was
reported in the survey by 20% of the nurses. This practice
may therefore represent a major area for improvement in
decreasing DIVM in the ICU in France.

In our study, healthcare cost associated with the 25
most discarded medications was evaluated at 1.64€ per
patient per ICU-day and more than 2,500,000€ annu-
ally. This is lower than the estimated cost of $1.9 (1.77€)
to $10.9 (10.15€) per case of anesthesia described in
the literature [27, 32]. However, this estimated annual
cost, which represents a minor share of annual health-
care expenditure in France, may have been under
evaluated in our study, as only the 25 most discarded
medications (based on volume measurement) have
been included in the estimated healthcare cost calcu-
lation. Thus, the financial implications could have sig-
nificantly differed if the calculation were based on the
cost of the most expensive drugs discarded rather than
the most discarded in volume. Moreover, we excluded
the additional costs of syringes, needles, solvents, pre-
ventable medical waste, and preparation time by the
nursing staff [22] from the cost analysis. These results
underline the need to adopt cost-effective practices
through waste reduction initiatives. In addition to
financial savings, these strategies to decrease DIVM
may present other advantages. Combating wastage by
optimizing medication preparation and administration
can help limit the risk of medications shortage in the
ICU, as the ones observed during the COVID-19 [33,
34]. It could also help decrease plastic use, which is
recognized as a major environmental pollutant having
direct negative impact on human health [35–37]. Thus,
the median number of plastic containers needed for the
administration of ICU medications was six per patient
per day of hospitalization, lower than the 10 syringes
(IQR, 4,5–18) per patient per 12-h shift thrown away

reported by Anstey et al.[38]. Nonetheless, we did not
evaluate syringe reuse nor include in this study the
many syringes used daily for "saline vectors" or for gas-
trointestinal tube administration.

We also acknowledge that our study presents several
limitations. First, we conducted a one-day observational
study, enrolling French ICUs on a voluntary basis, which
may have induced a self-selection bias driven by the
teams’ interest in sustainability. Indeed, this study was
performed right after the COVID-19 pandemic, when
the French healthcare system committed to reducing its
environmental impact. Nevertheless, it seems unlikely
that this recent political decision may have impacted the
caregivers’ practices on the study-day. Furthermore, since
data were collected on one chosen day over a 4-month
period in the different ICUs, the population described in
our study may not be representative of the overall popu-
lation of critically ill patients admitted to French ICUs.
Moreover, heterogeneity between centers is likely, par-
ticularly due to local protocols and practices. Indeed, dif-
ferent pharmaceutical dilution practices may exist across
the 81 participating ICUs, which could have influenced
the list of the 25 most discarded medications, as well as
the risk factors associated with DIVM. Ultimately, dif-
ference in practices may have impacted the estimated
annual cost of discarded pharmaceuticals for the French
health system. We also acknowledge that some patients
might have spent some time out of the ICU (OT, imag-
ing) on the study day, which was not accounted for in our
study. We did not include data on pharmaceutical vials,
although Jarrett et al. demonstrated that residual drug in
vials after reconstitution can be substantial [20]. Moreo-
ver, IV fluids waste were excluded from the study, espe-
cially for feasibility constraints. IV bag residual volume
is difficult to assess accurately without a precision scale.
Removal of the perfusion lines often makes the bag per-
meable, which would have required dedicated healthcare
providers to weight it just after removal. Although not
having a major direct environmental impact [39], resus-
citation fluids are largely used in critically ill patients and
represent important volumes of DIVM and plastic bags
or containers [39, 40]. We concede that this may have
resulted in an underestimation of DIMW. DIVM due to
CVC and peripheral perfusion replacement, or CVC tub-
ing change was not accounted for in our study, although
these hygiene associated limitations may generate medi-
cation waste [41–43]. Finally, the average price was cal-
culated from 3 different institutions where prices are
negotiated independently, with potential variations over
time that were not considered. The financial aspects of
wasted resources could therefore be more significant in
institutions or countries where drug prices are substan-
tially higher.
## Conclusions

Overall, this first large-scale study highlights the extent of DIVM in the ICU, as well as its contributing factors. To decrease DIVM, raising awareness of all the caregivers and implementing sustainable strategies in daily patient care are critical. Further research is therefore warranted to help integrate sustainable practices in the ICU, and may focus on drug residue disposal, resuscitation fluid waste (crystalloids and colloids), or drug preparation methods (volumes, dilutions, container types and sizes). These results may help building evidence-based ecode-sign of ICU healthcare, leading to human, environmental, and financial savings.

### Abbreviations

<table><tr><td>CI</td><td>Confidence interval</td></tr><tr><td>DIVM</td><td>Discarded intravenous medication</td></tr><tr><td>GHG</td><td>Greenhouse gases</td></tr><tr><td>ICU</td><td>Intensive care unit</td></tr><tr><td>IQR</td><td>Interquartile range</td></tr><tr><td>IRB</td><td>Institutional review board</td></tr><tr><td>IV</td><td>Intravenous</td></tr><tr><td>OR</td><td>Odds ratio</td></tr><tr><td>OT</td><td>Operating theater</td></tr><tr><td>SFAR</td><td>French society of anesthesia &amp; intensive care medicine</td></tr><tr><td>SOFA score</td><td>Sequential organ failure assessment score</td></tr><tr><td>RRT</td><td>Renal replacement therapy</td></tr></table>

## Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s13054-025-05299-6.

Additional file 1

Additional file 2

Additional file 3

### Acknowledgements

We thank Alice Blaizot and Nathalie Guichard, ICU registered nurses, for their contributions to the protocol development; Fabien Mitri, M.Sc., Sophie Lafond, Ph.D., Adèle Sichez, M.Sc., of the Délégation à la Recherche Clinique et à l'Innovation (DRCI) du Groupement Hospitalier de Territoire du Var (Centre Hospitalier Intercommunal Toulon La Seyne sur Mer), for their contributions to the protocol development and data monitoring; all investigators of the GAME OVER Study for their contribution; and Dr. Marjorie Bateman, M.D., for her help in proofreading some parts of the manuscript. None received compensation for their participation.

Chloé Allary, Laure Bonnet, Marie Bruyere, Erwan d'Aranda, Stéphanie Deryckere, Agnès Gendre, Marion Griton, Stéphane Fournier, Mehdi Hafiani, Florence Lallemant, Charlotte Martin, Jean-Claude Pauchard, Stéphanie Pons, Mathieu Schoeffler, Clémentine TACONET, Laurent Zieleskiewicz, Bernard Allaouchiche, Roland Amathieu, Emmanuel Besnier, Fanny Bounes, Belaid Bouhemad, Benjamin Chousterman, Olivier Collange, Claire Dahyot-Fizelier, Vincent Degos, Mathieu Desmard, Inès Lakbar, Yoann Launey, Jordi Miatello, Nicolas Mongardon, Jérôme Morel, Léa Satre Buisson, Pierre Trouiller, Hélène Beloeil, Marwan Bouras, Raphaël Cinotti, François Depret, Alexandre Godon, Alice Jacquens, Sébastien Kerever, Élodie Lang, Maxime Léger, Aurélien Mazeraud, Ludovic Muret, Vincent Pey, Céline Monard, Amélie Rolle, Stéphanie Sigaut

### Author Contributions

ED, SP, JC, EA, LB, CDF, FG, OC, EB, MS, NM, PE, MC, PJC contributed to the study conception and design. Acquisition, analysis, or interpretation of data were performed by all authors. The first draft of the manuscript was written by ED and SP. Critical revision of the manuscript was performed by JC, EA, CDF, TK,

PE, PJC performed the statistical analysis. Administrative and technical support were performed by RC and MC. All authors read and approved the final manuscript.

### Funding

This study was funded by the Centre Hospitalier Intercommunal de Toulon - La Seyne-sur-Mer for the database management and the sponsorship.

### Availability of data and materials

The first and the last authors had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The data that support the findings of this study are available from the corresponding author upon reasonable request.

## Declarations

### Ethics approval and consent to participate

The protocol was approved by an IRB on September 15, 2022 (Centre Hospitalier Intercommunal de Toulon - La Seyne-sur-Mer, France, IRB 12962). The study did not involve clinical follow-up. The database was approved by the sponsor's Data Protection Officer, in accordance with the European Union general data protection regulation. In accordance with French law, all the adult patients hospitalized in the participating ICU during the day of inclusion, or their next of kin if not able to consent, were informed of the study protocol and included if they did not express opposition to data collection.

### Consent for publication

Not applicable.

### Competing interest

SP received a mobility research grant from L'Institut Servier, outside of the submitted work.

### Author details

¹Intensive Care Unit, Sainte Anne Military Teaching Hospital, Toulon, France.

²DMU DREAM, Department of Anesthesiology and Critical Care, Sorbonne University GRC 29, AP-HP, Pitié-Salpêtrière, Paris, France. ³Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. ⁴Intensive Care Unit, Centre Hospitalier Intercommunal Toulon La Seyne-sur-Mer, Toulon, France.

⁵Clinical Research Unit, Délégation à la Recherche Clinique et à l'Innovation du GHT, Centre Hospitalier Intercommunal Toulon La Seyne-sur-Mer, Toulon, France. ⁶Intensive Care Department, DMU PARABOL, CHU Bichat-Claude Bernard, ⁷Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France. ⁸Department of Anesthesiology and Critical Care, Princess Grace Hospital, Monaco, Monaco. ⁹Department of Anaesthesia and Intensive Care, INSERM U1070, PHAR2, University Hospital of Poitiers, Poitiers, France. ¹⁰Medical Intensive Care Unit, Orléans Regional Hospital Center, Orléans, France. ¹¹Department of Anesthesia and Critical Care, Nouvel Hôpital Civil, Strasbourg University Hospitals, Strasbourg, France. ¹²Department of Anesthesia and Critical Care, INSERM U1096 - EnVI, Charles Nicolle University Hospital, Rouen, France.

¹²Intensive Care Unit, Montélimar Hospital - Groupe Hospitalier Portes de Provence, Montélimar, France. ¹³Department of Anesthesiology and Intensive Care Unit, Pasteur Clinic, Toulouse, France. ¹⁴Department of Anesthesiology, Sainte Anne Military Teaching Hospital, Toulon, France. ¹⁵Department of Anesthesiology and Intensive Care Medicine, Hôpital Nord, APHM, Marseille, France.

¹⁶Department of Anesthesia and Critical Care, Burn Center, Edouard Herriot University Hospital, Hospices Civils de Lyon, Lyon, France. ¹⁷Intensive Care Unit and Anesthesiology Department, Intensive Care Unit, Military Teaching Hospital Desgenettes, Lyon, France. ¹⁸Department of Anaesthesia and Critical Care, Nantes University Hospital, Nantes University, Hôtel Dieu, Nantes, France. ¹⁹UMR 1246 SPHERE "MethodS in Patients-Centered Outcomes and Health Research", University of Nantes, University of Tours, INSERM, IRS2 22 Boulevard Benoni Goulin, 44200 Nantes, France. ²⁰Hôpital d'Instruction des Armées Sainte Anne, Service de Réanimation, BP 600, 83800 Toulon Cedex 9, France.

Received: 28 November 2024 Accepted: 23 January 2025

Published online: 21 February 2025
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