---
title: "Net Positive Fluid Balance and Early Vancomycin Troughs in Critically Ill Patients"
id: "pubmed-42862327"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42862327"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42862327/"
doi: "10.1007/s00210-026-05974-7"
published_at: "2026-10-12T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Net Positive Fluid Balance and Early Vancomycin Troughs in Critically Ill Patients
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42862327
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42862327/)
- **DOI:** [10.1007/s00210-026-05974-7](https://doi.org/10.1007%2Fs00210-026-05974-7)
- **Published At:** 2026-10-12T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Retrospective cohort using MIMIC-IV ICU electronic health record data examined the relation between 24-hour **net positive fluid balance** and early vancomycin troughs. - Primary cohort included N = 255 ICU stays with timing-validated troughs, requiring ≥80% EMAR dose capture in prior 24 h and Δ serum creatinine ≤0.2 mg/dL in the 48 h before trough; troughs occurred within 72 h of first IV dose. - Primary exposure modeled per +5 L net fluid balance in the preceding 24 hours; outcome was natural-log transformed vancomycin trough concentration. - Multivariable models adjusted for serum creatinine, administered dose, and administration count in the prior 24 h. - Median observed trough was 14.00 mg/L (IQR 10.15–18.15); 62 of 255 troughs (24.3%) were <10 mg/L. - Point estimate indicated an 11.7% lower trough per +5 L (β = -0.1247; SE = 0.079; p = 0.115), but the 95% CI (–24.4% to +3.1%) included no association. - Serum creatinine showed a positive coefficient (β = 0.2995; p = 0.061) in adjusted models. - Sensitivity windows using troughs within 48 h (N = 162) and within 96 h (N = 289) produced similar point estimates; all confidence intervals included no association. - Exploratory analysis of **hypoalbuminemia** (<3 g/dL) was limited by missing data and small subgroup sizes, producing imprecise interaction estimates. - Authors framed results as hypothesis-generating and stated that prospective validation is required to determine whether fluid balance associates with early trough concentrations and **AUC** exposure.
## Clinical Analysis & Structured Key Points
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Online ahead of print. # Association of 24-hours net positive fluid balance with log-transformed vancomycin trough concentrations in the early phase of therapy among critically ill patients [Azfar Athar Ishaqui](https://pubmed.ncbi.nlm.nih.gov/?term=Ishaqui+AA&cauthor_id=42862327)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#full-view-affiliation-1 "Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia. azfar.hd@hotmail.com."), [Khalid Orayj](https://pubmed.ncbi.nlm.nih.gov/?term=Orayj+K&cauthor_id=42862327)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#full-view-affiliation-2 "Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia."), [Tauqeer Hussain Mallhi](https://pubmed.ncbi.nlm.nih.gov/?term=Mallhi+TH&cauthor_id=42862327)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#full-view-affiliation-3 "Discipline of Pharmacy, School of Dentistry & Medical Sciences, Charles Sturt University, Orange, NSW, Australia."), [Salman Ashfaq Ahmad](https://pubmed.ncbi.nlm.nih.gov/?term=Ahmad+SA&cauthor_id=42862327)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#full-view-affiliation-4 "Department of Pharmacy, Iqra University, Karachi, Pakistan."), [Sultan M Alshahrani](https://pubmed.ncbi.nlm.nih.gov/?term=Alshahrani+SM&cauthor_id=42862327)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#full-view-affiliation-2 "Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia."), [Rayah Asiri](https://pubmed.ncbi.nlm.nih.gov/?term=Asiri+R&cauthor_id=42862327)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#full-view-affiliation-2 "Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia."), [Adnan Iqbal](https://pubmed.ncbi.nlm.nih.gov/?term=Iqbal+A&cauthor_id=42862327)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#full-view-affiliation-5 "Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, Pakistan."), [Asaad Ahmed Asaad Khalil](https://pubmed.ncbi.nlm.nih.gov/?term=Khalil+AAA&cauthor_id=42862327)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#full-view-affiliation-6 "Quality and Performance Administration, Eastern Health Cluster, Ministry of Health, Dammam, Saudi Arabia."), [Mohammed Ali Kaddoura](https://pubmed.ncbi.nlm.nih.gov/?term=Kaddoura+MA&cauthor_id=42862327)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#full-view-affiliation-7 "Clinical Excellence Administration, King Fahad Specialist Hospital, Dammam, Saudi Arabia."), [Muhammad Bilal Maqsood](https://pubmed.ncbi.nlm.nih.gov/?term=Maqsood+MB&cauthor_id=42862327)[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#full-view-affiliation-8 "Quality and Performance Administration, Eastern Health Cluster, Health Holding Company, Dammam, Saudi Arabia."), [Javeria Farooq](https://pubmed.ncbi.nlm.nih.gov/?term=Farooq+J&cauthor_id=42862327)[ 9 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#full-view-affiliation-9 "Department of Pharmacognosy, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, Pakistan."), [Narendar Kumar](https://pubmed.ncbi.nlm.nih.gov/?term=Kumar+N&cauthor_id=42862327)[ 10 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#full-view-affiliation-10 "Department of Pharmacy Practice, Faculty of Pharmacy, University of Sindh, Jamshoro, Pakistan.") Affiliations Expand ### Affiliations * 1 Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia. azfar.hd@hotmail.com. * 2 Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia. * 3 Discipline of Pharmacy, School of Dentistry & Medical Sciences, Charles Sturt University, Orange, NSW, Australia. * 4 Department of Pharmacy, Iqra University, Karachi, Pakistan. * 5 Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, Pakistan. * 6 Quality and Performance Administration, Eastern Health Cluster, Ministry of Health, Dammam, Saudi Arabia. * 7 Clinical Excellence Administration, King Fahad Specialist Hospital, Dammam, Saudi Arabia. * 8 Quality and Performance Administration, Eastern Health Cluster, Health Holding Company, Dammam, Saudi Arabia. * 9 Department of Pharmacognosy, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, Pakistan. * 10 Department of Pharmacy Practice, Faculty of Pharmacy, University of Sindh, Jamshoro, Pakistan. * PMID: **42862327** * DOI: [ 10.1007/s00210-026-05974-7 ](https://doi.org/10.1007/s00210-026-05974-7) Item in Clipboard # Association of 24-hours net positive fluid balance with log-transformed vancomycin trough concentrations in the early phase of therapy among critically ill patients Azfar Athar Ishaqui et al. Naunyn Schmiedebergs Arch Pharmacol. 2026. Show details Display options Display options Format Abstract PubMed PMID Naunyn Schmiedebergs Arch Pharmacol Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Naunyn+Schmiedebergs+Arch+Pharmacol%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Naunyn+Schmiedebergs+Arch+Pharmacol%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42862327/) . 2026 Oct 12. doi: 10.1007/s00210-026-05974-7. Online ahead of print. ### Authors [Azfar Athar Ishaqui](https://pubmed.ncbi.nlm.nih.gov/?term=Ishaqui+AA&cauthor_id=42862327)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#short-view-affiliation-1 "Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia. azfar.hd@hotmail.com."), [Khalid Orayj](https://pubmed.ncbi.nlm.nih.gov/?term=Orayj+K&cauthor_id=42862327)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#short-view-affiliation-2 "Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia."), [Tauqeer Hussain Mallhi](https://pubmed.ncbi.nlm.nih.gov/?term=Mallhi+TH&cauthor_id=42862327)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#short-view-affiliation-3 "Discipline of Pharmacy, School of Dentistry & Medical Sciences, Charles Sturt University, Orange, NSW, Australia."), [Salman Ashfaq Ahmad](https://pubmed.ncbi.nlm.nih.gov/?term=Ahmad+SA&cauthor_id=42862327)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#short-view-affiliation-4 "Department of Pharmacy, Iqra University, Karachi, Pakistan."), [Sultan M Alshahrani](https://pubmed.ncbi.nlm.nih.gov/?term=Alshahrani+SM&cauthor_id=42862327)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#short-view-affiliation-2 "Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia."), [Rayah Asiri](https://pubmed.ncbi.nlm.nih.gov/?term=Asiri+R&cauthor_id=42862327)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#short-view-affiliation-2 "Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia."), [Adnan Iqbal](https://pubmed.ncbi.nlm.nih.gov/?term=Iqbal+A&cauthor_id=42862327)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#short-view-affiliation-5 "Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, Pakistan."), [Asaad Ahmed Asaad Khalil](https://pubmed.ncbi.nlm.nih.gov/?term=Khalil+AAA&cauthor_id=42862327)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#short-view-affiliation-6 "Quality and Performance Administration, Eastern Health Cluster, Ministry of Health, Dammam, Saudi Arabia."), [Mohammed Ali Kaddoura](https://pubmed.ncbi.nlm.nih.gov/?term=Kaddoura+MA&cauthor_id=42862327)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#short-view-affiliation-7 "Clinical Excellence Administration, King Fahad Specialist Hospital, Dammam, Saudi Arabia."), [Muhammad Bilal Maqsood](https://pubmed.ncbi.nlm.nih.gov/?term=Maqsood+MB&cauthor_id=42862327)[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#short-view-affiliation-8 "Quality and Performance Administration, Eastern Health Cluster, Health Holding Company, Dammam, Saudi Arabia."), [Javeria Farooq](https://pubmed.ncbi.nlm.nih.gov/?term=Farooq+J&cauthor_id=42862327)[ 9 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#short-view-affiliation-9 "Department of Pharmacognosy, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, Pakistan."), [Narendar Kumar](https://pubmed.ncbi.nlm.nih.gov/?term=Kumar+N&cauthor_id=42862327)[ 10 ](https://pubmed.ncbi.nlm.nih.gov/42862327/#short-view-affiliation-10 "Department of Pharmacy Practice, Faculty of Pharmacy, University of Sindh, Jamshoro, Pakistan.") ### Affiliations * 1 Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia. azfar.hd@hotmail.com. * 2 Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia. * 3 Discipline of Pharmacy, School of Dentistry & Medical Sciences, Charles Sturt University, Orange, NSW, Australia. * 4 Department of Pharmacy, Iqra University, Karachi, Pakistan. * 5 Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, Pakistan. * 6 Quality and Performance Administration, Eastern Health Cluster, Ministry of Health, Dammam, Saudi Arabia. * 7 Clinical Excellence Administration, King Fahad Specialist Hospital, Dammam, Saudi Arabia. * 8 Quality and Performance Administration, Eastern Health Cluster, Health Holding Company, Dammam, Saudi Arabia. * 9 Department of Pharmacognosy, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, Pakistan. * 10 Department of Pharmacy Practice, Faculty of Pharmacy, University of Sindh, Jamshoro, Pakistan. * PMID: **42862327** * DOI: [ 10.1007/s00210-026-05974-7 ](https://doi.org/10.1007/s00210-026-05974-7) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## Abstract Early vancomycin troughs are frequently low in critical illness and fluid accumulation may contribute through distribution effects. This study estimated the association between net positive fluid balance and early vancomycin troughs as a hypothesis-generating analysis and explored variation across early-therapy windows and by hypoalbuminemia. A retrospective cohort study used ICU electronic health record data from MIMIC-IV. ICU stays with a timing-validated trough were included. The primary cohort N = 255 required at least 80% EMAR dose capture in the prior 24 h and delta serum creatinine at or below 0.2 mg/dL across the 48 h before trough and trough within 72 h of first IV dose. Net fluid balance in the prior 24 h was modeled per + 5 L. Outcome was log trough. Models adjusted for serum creatinine and administered dose and administration count in the prior 24 h. Sensitivity windows were within 48 h (N = 162) and within 96 h (N = 289). Hypoalbuminemia below 3 g/dL was explored in the measured subset. Median trough was 14.00 mg/L (IQR 10.15 to 18.15) and 62 of 255 were below 10 mg/L (24.3%). The point estimate suggested an 11.7% lower trough concentration per + 5 L net positive balance (β = - 0.1247; SE = 0.079; p = 0.115), but the 95% CI (- 24.4% to + 3.1%) included no association. Serum creatinine had a positive coefficient (β = 0.2995; p = 0.061). Point estimates were similar across early-therapy windows with all confidence intervals including no association. The exploratory albumin interaction was imprecise and limited by substantial missingness and small subgroup sizes. The point estimate suggested lower early vancomycin troughs with higher net positive fluid balance, but the confidence interval included no association. These hypothesis-generating findings require prospective validation to clarify whether fluid balance is associated with early trough concentrations and area under the curve exposure. **Keywords:** Critical illness; Fluid balance; Hypoalbuminemia; Intensive care unit; Net positive fluid balance; Pharmacokinetics; Trough concentration; Vancomycin. © 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Consent for publication: All authors have agreed to the publication of this study. Ethics approval and consent to participate: This study used deidentified MIMIC-IV data. The collection of patient information and creation of the database were reviewed by the Beth Israel Deaconess Medical Center Institutional Review Board which approved the data-sharing initiative and waived informed consent. Competing interests: The authors declare no competing interests. Clinical trial number: Not applicable. ## References 1. 1. Abraham J, Sinnollareddy MG, Roberts MS, Williams P, Peake SL, Lipman J, Roberts JA (2019) Plasma and interstitial fluid population pharmacokinetics of vancomycin in critically ill patients with sepsis. Int J Antimicrob Agents 53(2):137–142 - [DOI](https://doi.org/10.1016/j.ijantimicag.2018.09.021) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/30296581/) 2. 1. Al Sulaiman K, Alshaya A, Aljuhani O, Alsaeed A, Alshehri N, Vishwakarma R, Alzahrani H, Althewaibi S, Alghamdi N, Alhelal K (2021) The impact of early target attainment of vancomycin in critically ill patients with confirmed Gram-positive infection: a retrospective cohort study. BMC Infect Dis 21(1) - [DOI](https://doi.org/10.1186/s12879-021-06840-y) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/34819023/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/8613993/) 3. 1. Aljutayli A, Thirion DJ, Nekka F (2022) Critical assessment of the revised guidelines for vancomycin therapeutic drug monitoring. Biomed Pharmacother 155 - [DOI](https://doi.org/10.1016/j.biopha.2022.113777) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/36271558/) 4. 1. Baptista JP, Sousa E, Martins PJ, Pimentel JM (2012) Augmented renal clearance in septic p
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