‘‘Sugar for the Heart’’, a bitter pill for tenecteplase: the crystallisation trap of pre-hospital fibrinolysis

Abstract

Background

Recent evidence suggests that empiric prehospital administration of tenecteplase in out-of-hospital cardiac arrest is associated with decreased survival and lower rates of return of spontaneous circulation. While diagnostic uncertainty is a primary factor, operational hazards in austere environments must also be examined.

Main body of the abstract

This comment explores an underappreciated and potentially lethal operational hazard: the immediate chemical incompatibility between tenecteplase and dextrose-containing solutions. In chaotic pre-hospital settings, clinicians often rely on the cognitive heuristic of using dextrose lines to limit sodium intake, especially during cardiac emergencies. However, mixing tenecteplase with dextrose triggers instant crystallization and line occlusion. This effectively denies the patient the fibrinolytic agent while simultaneously compromising a critical intravenous access. To mitigate this risk, we propose three clinical safety barriers: physical segregation of dextrose from acute coronary syndrome kits, the mandatory implementation of a 20-mL normal saline flush before and after administration, and the use of point-of-care cognitive aids on drug packaging.

Conclusion

Addressing the complex outcomes of prehospital thrombolysis requires mitigating simple, yet catastrophic, chemical errors. Environmental design and strict operational protocols are essential to ensure the safe delivery of tenecteplase in the field.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13049-026-01594-5.

Background

Cowley et al. [1] recently reported decreased survival and return of spontaneous circulation (ROSC) associated with empiric prehospital tenecteplase (TNK) in out-of-hospital cardiac arrest. While diagnostic uncertainty undoubtedly plays a major role in these complex outcomes, we propose that an underappreciated operational hazard—inadvertent chemical incompatibility—might also contribute to real-world therapeutic failures in such chaotic environments.

As TNK supplants alteplase as the standard of care for pre-hospital fibrinolysis [2]—supported by the ASSENT-2 trial demonstrating equivalent mortality with superior ease of administration [3]—a dangerous safety gap has emerged.

Main text

While alteplase carries strict dilution restrictions, tenecteplase presents an immediate and severe chemical incompatibility with dextrose-containing solutions. Although the Summary of Product Characteristics (SmPC) notes this contraindication, the immediate physical consequence—precipitation and line crystallization—is often buried in technical documentation [4]. To our knowledge, no specific clinical case reports describe the operational failure (e.g., immediate line occlusion) in the field, suggesting a significant gap in reporting and awareness.

In the high-stakes environment of pre-hospital care and resuscitation, providers often operate under "System 1" thinking. A dangerous cognitive trap occurs when managing cardiac emergencies or ST-elevation myocardial infarction (STEMI) complicated by acute pulmonary edema. Clinicians frequently prioritize dextrose (e.g., D5W) as "keep-vein-open" lines to limit sodium intake. This "Sugar for the Heart" heuristic creates a lethal setup for TNK administration: contact with dextrose triggers immediate opalescence and precipitation, rendering the drug inert and potentially causing catheter occlusion or particulate embolization.

If this crystallization occurs during an active resuscitation as described in Cowley et al.’s cohort, the patient is effectively denied the fibrinolytic agent while a critical intravenous access line is simultaneously compromised.

To mitigate this risk, we propose three clinical safety barriers:

• Physical Segregation: Only 0.9% normal saline or sterile water should be stocked within acute coronary syndrome-specific kits, with dextrose sequestered in metabolic or hypoglycemia kits.

• Mandatory "Saline Bridge": To prevent line occlusion, clinicians must implement a strict 20-mL 0.9% normal saline flush both immediately before and after TNK administration. This volume is critical to fully clear the "dead space" of the intravenous tubing of any residual dextrose, regardless of the primary infusion running.

• Point-of-Care Cognitive Aids: Bold warning labels should be affixed directly to TNK packaging (Fig. 1), and training must explicitly "un-teach" the historical use of glucose lines during cardiac emergencies when TNK is the fibrinolytic agent of choice.

Fig. 1.

Proposed Point-of-Care Safety Label for Remote Medical Kits. A cognitive aid designed to mitigate the risk of therapeutic error associated with the "Sugar for the Heart" heuristic. This label highlights the immediate chemical incompatibility of tenecteplase with dextrose solutions, promoting a "Zero-Dextrose" approach during the acute phase

Conclusions

We must ensure that environmental design and cognitive aids prevent pharmacological progress from being sabotaged by simple chemical errors. Recognizing and preventing the crystallization trap of tenecteplase is a critical step in improving the safety and efficacy of prehospital resuscitation protocols.

Abbreviations

ROSC

Return of spontaneous circulation

SmPC

Summary of Product Characteristics

STEMI

ST-elevation myocardial infarction

TNK

Tenecteplase

Authors’ contributions

TP conceptualized the manuscript and drafted the initial text. AA and GM critically reviewed and revised the manuscript for important intellectual content. All authors read and approved the final manuscript.

Funding

The authors declare that no funding was received for this work.

Data availability

Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.