Is There a Norepinephrine Dose Threshold for Safe Intrahospital Transport in Critically Ill Patients with Sepsis?
Introduction: Intrahospital transport (IHT) may expose critically ill patients with sepsis to hemodynamic deterioration, respiratory compromise, and interruption of life-sustaining therapies during necessary diagnostic procedures outside the controlled intensive care unit environment itself. Current recommendations emphasize stabilization, continuous monitoring, trained personnel, and individualized risk–benefit assessment but provide no evidence-based norepinephrine threshold for transport eligibility. In our practice, transport is generally deferred when norepinephrine exceeds 1.0 μg/kg/min, whereas 0.5–1.0 μg/kg/min represents a gray zone requiring cautious individualized assessment. These institutional limits remain unvalidated. We hypothesized that a clinically meaningful norepinephrine threshold for safe IHT exists.
Materials and Methods: A PubMed search identified guidelines and systematic reviews addressing adult IHT, sepsis, norepinephrine dose, cardiovascular failure, mortality, and transport-related adverse events. Reported dose categories were examined for their potential relevance to transport decisions.
Results: Current recommendations base transport eligibility on physiological stability, vasopressor dose trend, respiratory support, monitoring capability, team expertise, and anticipated clinical benefit. Norepinephrine cutoffs of 0.2 and 0.4 μg/kg/min have been proposed to distinguish low, intermediate, and high cardiovascular failure severity. Mortality rises progressively with increasing norepinephrine exposure, and a maximum dose above 1.0 μg/kg/min has been associated with higher early mortality in circulatory shock. However, these values were developed for severity stratification and prognostication rather than transport safety. No guideline or clinical study has validated either 0.5 or 1.0 μg/kg/min as an IHT threshold.
Discussion and Conclusion: Norepinephrine dose may be a marker of transport-related physiological vulnerability. Prospective multicenter studies are needed to determine a clinically useful norepinephrine threshold for the intrahospital transport of critically ill patients with sepsis.
Keywords: Hemodynamic instability, Intrahospital transport, Norepinephrine, Sepsis
References
Zhang YB, Ma D, Li R, Wei YJ, Wang XY, Sun Y, Zhang X, Liu Y, Wang J, Wang SY. A Critical Review and Evidence Mapping of Guidelines for Transport of Critically Ill Patients. Nurs Crit Care. 2025 Jul;30(4):e70124. doi: 10.1111/nicc.70124. PMID: 40717028.
Pölkki A, Pekkarinen PT, Hess B, Blaser AR, Bachmann KF, Lakbar I, Hollenberg SM, Lobo SM, Rezende E, Selander T, Reinikainen M. Noradrenaline dose cutoffs to characterise the severity of cardiovascular failure: Data-based development and external validation. Acta Anaesthesiol Scand. 2024 Nov;68(10):1400-1408. doi: 10.1111/aas.14519. Epub 2024 Aug 30. PMID: 39210783.
Reinikainen M, Delamarre L, Blaser AR, Hollenberg SM, Lobo SM, Rezende E, Moreno R, Rhodes A, Ranzani OT, Singer M, Lakbar I. Association of noradrenaline dose with mortality in critically ill patients: a systematic review and dose-response meta-analysis. Crit Care. 2025 Nov 20;29(1):498. doi: 10.1186/s13054-025-05717-9. PMID: 41267052; PMCID: PMC12632045.
Zirpe KG, Tiwari AM, Kulkarni AP, Govil D, Samavedam S, Sharma J, Dixit SB, Munjal M, Sinha S, Singh YP, Sumalatha A, Kaurgayala SD, Chandankhede SR, Ahmed S, Bandyopadhyay S, Karanth S, Mishra V, Dongre A, Gupta B, Routray P, Nongthombam R, Jagiasi B, Bhattacharya P, Todi S. Position Statement of ISCCM on Intrahospital Transport of Critically Ill Patients. Indian J Crit Care Med. 2025 Apr;29(4):291-300. doi: 10.5005/jp-journals-10071-24939. PMID: 40322228; PMCID: PMC12045056.
Ceausu D, Boulet N, Roger C, Alonso S, Lefrant JY, Boisson C, Mura T, Muller L. CRITICAL NOREPINEPHRINE DOSE TO PREDICT EARLY MORTALITY DURING CIRCULATORY SHOCK IN INTENSIVE CARE: A RETROSPECTIVE STUDY IN 3423 ICU PATIENTS OVER 4-YEAR PERIOD. Shock. 2024 Nov 1;62(5):682-687. doi: 10.1097/SHK.0000000000002454. Epub 2024 Aug 28. PMID: 39193888.
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The Prescription-to-Administration Interval: A Proposed Quality Indicator for Sepsis Care in Surgical Intensive Care Units
Mehmet Eren Yuksel
Ankara Etlik City Hospital, Surgical Intensive Care Unit
INTRODUCTION / OBJECTIVE
Early antimicrobial treatment is a key part of sepsis management. In practice, however, the time recorded in the medical chart may reflect when an antibiotic was prescribed rather than when it was actually administered. Delays can occur after the order is written because of pharmacy preparation, medication transport, staffing, or bedside workflow. This report draws attention to that gap and proposes the prescription-to-administration interval as a potential quality indicator in sepsis care.
CASE
The idea arose during an independent medico-legal expert review of a postoperative intensive care patient whose family claimed that delayed antibiotic treatment had contributed to the patient's death. The medical records contained a handwritten physician order for antimicrobial therapy approximately two hours after admission. Based on the documented clinical condition and the sepsis recommendations relevant to the case, the decision to prescribe antimicrobial therapy was considered timely. What could not be clearly determined from the records was when the first dose was actually given. This raised a simple but important question: after an antibiotic is prescribed, how long does it take before it reaches the patient? Several steps occur between prescription and bedside administration, including pharmacy preparation, transport to the intensive care unit, and nursing administration. Each step can add delay. The purpose of this report is not to reevaluate the individual clinical case, but to highlight this often overlooked part of the medication-delivery process.
DISCUSSION / CONCLUSION
A timely prescription does not always mean timely administration. When only the prescription time is recorded or reviewed, delays occurring later in the medication-delivery process may remain unnoticed. We therefore propose routinely recording the prescription-to-administration interval in patients with suspected sepsis. This simple measure could help identify where delays occur and whether they are related to pharmacy processing, medication transport, staffing, or bedside workflow. Used prospectively, this interval may serve as a practical patient-safety and quality indicator and provide a more complete picture of antimicrobial timeliness than prescription time alone. Further studies are needed to define typical intervals, identify preventable delays, and determine whether longer intervals are associated with clinical outcomes.
Keywords: Antibiotic administration, Medication delay, Patient safety, Quality indicator, Sepsis
References:
1. Taylor SP, Kowalkowski MA, Skewes S, Chou SH. Real-World Implications of Updated Surviving Sepsis Campaign Antibiotic Timing Recommendations. Crit Care Med. 2024 Jul 1;52(7):1002-1006. doi: 10.1097/CCM.0000000000006240. Epub 2024 Feb 22. PMID: 38385751.
2. Kim RY, Ng AM, Persaud AK, Furmanek SP, Kothari YN, Price JD, Wiemken TL, Saad MA, Guardiola JJ, Cavallazzi RS. Antibiotic Timing and Outcomes in Sepsis. Am J Med Sci. 2018 Jun;355(6):524-529. doi: 10.1016/j.amjms.2018.02.007. Epub 2018 Feb 21. PMID: 29891035.
3. Cullen M, Fogg T, Delaney A. Timing of appropriate antibiotics in patients with septic shock: a retrospective cohort study. Emerg Med Australas. 2013 Aug;25(4):308-15. doi: 10.1111/1742-6723.12100. Epub 2013 Jul 21. PMID: 23911021.
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FDA-Approved Labeling Limits Dexmedetomidine Infusion to 24 Hours: Why Is It Used Longer in Patients With Sepsis?
Mehmet Eren Yuksel
Ankara Etlik City Hospital, Surgical Intensive Care Unit
Introduction: Dexmedetomidine is often used for light and cooperative sedation in mechanically ventilated patients with sepsis. However, US Food and Drug Administration-approved labeling limits continuous ICU infusion to 24 hours. The Turkish prescribing information also states that infusion should not exceed 24 hours. Despite this limit, dexmedetomidine is frequently used for longer periods. This study examined the evidence behind this difference between drug labeling and clinical practice.
Materials and Methods: A literature-based study was conducted using official prescribing information, PubMed-indexed clinical trials, prolonged-infusion studies, and practice guidelines. Studies involving adults with sepsis or prolonged mechanical ventilation were evaluated. The main outcomes were infusion duration, sedation quality, mortality, ventilator-free days, and adverse events.
Results: Several major studies used dexmedetomidine for longer than 24 hours. In MENDS2, study medication was given for a median of 3 days. Dexmedetomidine and propofol produced similar results for delirium- or coma-free days, ventilator-free days, and 90-day mortality. DESIRE found no significant improvement in mortality or ventilator-free days. MIDEX and PRODEX showed that dexmedetomidine was not inferior to midazolam or propofol for maintaining target sedation during prolonged mechanical ventilation. DecatSepsis used dexmedetomidine for 48 hours but did not establish a mortality benefit. Bradycardia and hypotension remained important adverse effects.
Discussion: Use beyond 24 hours is off-label, but it is not automatically prohibited. Prolonged use may be considered when ongoing sepsis requires extended mechanical ventilation and continued light, cooperative sedation, particularly when deeper sedation is undesirable. Potential benefits should be balanced against bradycardia, hypotension, cardiovascular intolerance, and the absence of a proven mortality benefit. Therefore, prolonged treatment should be individualized according to sedation requirements, expected clinical benefit, hemodynamic tolerance, and available alternatives. Close monitoring, daily reassessment, clinical justification, and clear documentation are essential.
Conclusion: Prolonged dexmedetomidine infusion in sepsis is an evidence-informed but off-label practice. It may be appropriate in selected, closely monitored patients when the expected sedation benefit outweighs cardiovascular risk. Current evidence does not support routine prolonged use in every patient or demonstrate a mortality benefit.
Keywords: Dexmedetomidine, Off-Label Use, Sedation, Sepsis
References
1. FDA. Dexmedetomidine prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/206628s017lbl.pdf
2. Ezz Al-Regal AR, Ramzy EA, Atia AAA, Emara MM. Dexmedetomidine for Reducing Mortality in Patients With Septic Shock: A Randomized Controlled Trial (DecatSepsis). Chest. 2024;166(6):1394-1405. doi:10.1016/j.chest.2024.06.3794. PMID: 39004217.
3. Hughes CG, Mailloux PT, Devlin JW, et al.; MENDS2 Study Investigators. Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis. N Engl J Med. 2021;384(15):1424-1436. doi:10.1056/NEJMoa2024922. PMID: 33528922.
4. Jakob SM, Ruokonen E, Grounds RM, et al.; Dexmedetomidine for Long-Term Sedation Investigators. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012;307(11):1151-1160. doi:10.1001/jama.2012.304. PMID: 22436955.
5. Kawazoe Y, Miyamoto K, Morimoto T, et al.; DESIRE Trial Investigators. Effect of Dexmedetomidine on Mortality and Ventilator-Free Days in Patients Requiring Mechanical Ventilation With Sepsis: A Randomized Clinical Trial. JAMA. 2017;317(13):1321-1328. doi:10.1001/jama.2017.2088. PMID: 28322414.
6. Møller MH, Alhazzani W, Lewis K, et al. Use of dexmedetomidine for sedation in mechanically ventilated adult ICU patients: a rapid practice guideline. Intensive Care Med. 2022;48(7):801-810. doi:10.1007/s00134-022-06660-x. PMID: 35587274.
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