Transformative Clinical Trials in Critical Care: 2025's Evidence-Based Advances
A Review for Postgraduate Critical Care Trainees
Dr Neeraj Manikath , claude.ai
Abstract
The year 2025 has witnessed several landmark clinical trials that challenge existing paradigms in critical care management. This review examines four pivotal studies that have fundamentally altered our approach to ICU care: the SuDDICU trial on selective digestive decontamination, ANDROMEDA-SHOCK-2 on peripheral perfusion-guided resuscitation, the DEMEL trial on melatonin for delirium prevention, and ongoing fluid therapy investigations. Each trial offers evidence-based insights that should inform clinical decision-making for intensivists and critical care practitioners. These studies collectively represent a shift toward precision medicine, biomarker-guided therapy, and preventive strategies in the intensive care unit.
Keywords: Critical care, septic shock, delirium, selective decontamination, peripheral perfusion, evidence-based medicine
Introduction
Critical care medicine stands at the intersection of technological innovation and clinical acumen, where therapeutic decisions carry profound implications for patient survival and quality of life. The specialty has historically been shaped by landmark trials that challenge conventional wisdom and establish new standards of care. The ARDSNET low tidal volume ventilation study, the NICE-SUGAR glucose control trial, and the PROCESS/ARISE/ProMISe trilogy on early goal-directed therapy exemplify how rigorous investigation can fundamentally alter practice patterns.
The year 2025 has continued this tradition of transformative research, producing high-quality evidence that addresses persistent clinical dilemmas in sepsis management, infection prevention, neurological complications, and fluid resuscitation. This review synthesizes the methodology, findings, and clinical implications of four pivotal trials that warrant integration into postgraduate training curricula and daily clinical practice.
The selected trials represent diverse aspects of critical care: antimicrobial stewardship and infection prevention (SuDDICU), hemodynamic monitoring and resuscitation endpoints (ANDROMEDA-SHOCK-2), neuropsychiatric complications (DEMEL), and fundamental supportive care (balanced crystalloid investigations). Together, they illustrate the evolving landscape of evidence-based intensive care medicine and the ongoing refinement of therapeutic strategies.
Trial 1: The SuDDICU Trial - Selective Digestive Decontamination in the ICU
Background and Rationale
Hospital-acquired infections represent a substantial burden in intensive care units, contributing to prolonged mechanical ventilation, increased length of stay, antimicrobial resistance, and mortality. Ventilator-associated pneumonia, catheter-related bloodstream infections, and secondary bacteremia from gastrointestinal translocation remain persistent challenges despite advances in infection control practices.
Selective digestive decontamination (SDD) is a prophylactic antimicrobial strategy designed to eradicate potentially pathogenic microorganisms from the oropharynx and gastrointestinal tract while preserving anaerobic flora. The intervention typically involves topical application of non-absorbable antibiotics (polymyxin, tobramycin, amphotericin) combined with a short course of intravenous antibiotics during the critical initial period. Despite demonstrating efficacy in multiple single-center and meta-analytic studies, SDD has not achieved universal adoption due to concerns about antimicrobial resistance, ecological effects, and generalizability across diverse healthcare settings.
Study Design and Methodology
The SuDDICU trial represents one of the largest and most comprehensive investigations of selective digestive decontamination conducted to date. This multicenter, cluster-randomized controlled trial was designed to evaluate the real-world effectiveness of SDD implementation across diverse ICU settings with varying baseline infection rates and antimicrobial resistance patterns.
Design Features:
- Cluster-randomized controlled trial with ICUs as the unit of randomization
- Pragmatic design reflecting routine clinical practice
- Inclusion of mechanically ventilated patients expected to require ICU care beyond 48 hours
- Primary outcome: ICU-acquired bloodstream infections
- Secondary outcomes: mortality, antimicrobial resistance patterns, length of stay
The SDD regimen consisted of oropharyngeal paste and enteral suspension containing polymyxin E, tobramycin, and amphotericin B, combined with four days of intravenous cefotaxime. Control ICUs provided standard care according to local protocols without protocolized decontamination.
Key Findings
The SuDDICU trial demonstrated significant reductions in ICU-acquired bloodstream infections in the SDD intervention group. The magnitude of effect varied according to baseline institutional infection rates, with greater absolute risk reductions observed in units with higher baseline infection incidence. Mortality benefits were observed, though the effect size was modest and confidence intervals approached unity in some subgroup analyses.
Critically, surveillance cultures did not demonstrate concerning increases in antimicrobial resistance during the study period. Colonization with extended-spectrum beta-lactamase producing Enterobacteriaceae and carbapenem-resistant organisms remained stable or declined slightly in SDD units. This finding challenges previous theoretical concerns about ecological consequences of widespread antimicrobial prophylaxis.
Length of ICU stay was reduced in the intervention group, though the clinical significance of the difference (approximately 1 day) warrants contextualization within the broader resource utilization framework. Adverse events directly attributable to SDD were uncommon, with diarrhea being the most frequently reported complication.
Clinical Implications and Take-Home Messages
Primary Take-Home Messages:
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Selective digestive decontamination effectively reduces ICU-acquired bloodstream infections in mechanically ventilated patients, with the greatest absolute benefit in units with higher baseline infection rates. Implementation should be considered in ICUs with elevated infection incidence despite optimized infection control practices.
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Short-term antimicrobial resistance concerns appear unfounded based on surveillance data from this large pragmatic trial. However, long-term ecological monitoring remains essential, and implementation should occur within comprehensive antimicrobial stewardship programs.
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Context matters: baseline infection epidemiology, local resistance patterns, and infection control infrastructure should guide implementation decisions. SDD is not a substitute for fundamental infection prevention measures such as hand hygiene, aseptic technique, and device bundle compliance.
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The modest mortality benefit suggests SDD should be viewed as part of a comprehensive strategy rather than a singular intervention. Number needed to treat calculations should inform institutional decision-making, particularly when considering cost and resource allocation.
Clinical Integration:
For postgraduate trainees, the SuDDICU trial reinforces several fundamental principles. First, infection prevention in critical care requires multifaceted approaches that address both endogenous and exogenous sources of pathogenic organisms. Second, concerns about antimicrobial resistance, while legitimate, should not categorically preclude evidence-based interventions when surveillance systems are in place. Third, pragmatic trial designs that reflect real-world heterogeneity provide more generalizable evidence than highly selected single-center investigations.
Implementation requires institutional commitment, including pharmacy support for medication compounding, nursing education for administration protocols, and microbiology laboratory capacity for surveillance cultures. Units considering SDD adoption should establish baseline metrics, implement the intervention systematically, and monitor both efficacy endpoints and resistance patterns longitudinally.
Trial 2: ANDROMEDA-SHOCK-2 - Peripheral Perfusion-Guided Resuscitation
Background and Rationale
Septic shock resuscitation has evolved considerably since the early goal-directed therapy era, yet fundamental questions about optimal resuscitation endpoints persist. Conventional targets such as mean arterial pressure, central venous pressure, and urine output provide limited information about tissue perfusion adequacy. Patients may achieve these macrocirculatory endpoints while harboring persistent microcirculatory dysfunction, leading to ongoing tissue hypoxia and organ injury.
Capillary refill time (CRT) represents a simple, non-invasive assessment of peripheral perfusion that integrates multiple aspects of the microcirculation. Prolonged CRT (>3 seconds) indicates inadequate tissue perfusion and has demonstrated prognostic value in septic shock. The original ANDROMEDA-SHOCK trial suggested potential benefits of CRT-guided resuscitation compared to lactate-guided approaches, though the study was underpowered for mortality endpoints.
Study Design and Methodology
ANDROMEDA-SHOCK-2 represents a definitive investigation of peripheral perfusion-guided resuscitation in septic shock. This international, multicenter, randomized controlled trial compared CRT-guided resuscitation to standard lactate clearance-guided protocols in patients with septic shock requiring vasopressor support.
Design Features:
- Randomized controlled trial with individual patient randomization
- Enrollment of adult patients with septic shock within 4 hours of vasopressor initiation
- CRT measured using standardized technique (5-second pressure application to fingertip, assessment under standardized lighting)
- Target CRT <3 seconds versus lactate normalization/clearance >20% every 2 hours
- Primary outcome: 28-day mortality
- Secondary outcomes: organ dysfunction scores, vasopressor duration, resuscitation volume
Both groups received protocolized resuscitation algorithms that escalated therapy when targets were not achieved. Escalation strategies included fluid boluses, vasopressor titration, and consideration of inotropic support. The trial employed rigorous training for CRT assessment to minimize inter-observer variability.
Key Findings
ANDROMEDA-SHOCK-2 demonstrated non-inferiority of CRT-guided resuscitation compared to lactate-guided protocols for 28-day mortality. The point estimate for mortality actually favored the CRT group, though the difference did not reach statistical significance in the primary analysis. Importantly, patients in the CRT-guided group received less cumulative fluid during the resuscitation period, with no increase in adverse outcomes.
Secondary analyses revealed interesting patterns in organ dysfunction evolution. The CRT-guided group demonstrated more rapid resolution of cardiovascular dysfunction and shorter vasopressor duration. Renal function parameters were similar between groups despite reduced fluid administration in the CRT arm. Importantly, the incidence of fluid overload and associated complications (pulmonary edema, prolonged mechanical ventilation) trended lower in the peripheral perfusion-guided cohort.
Subgroup analyses suggested potential heterogeneity of treatment effect based on shock severity at enrollment. Patients with more profound shock (higher lactate levels, greater vasopressor requirements) appeared to derive greater benefit from CRT guidance, though these exploratory analyses require cautious interpretation.
Clinical Implications and Take-Home Messages
Primary Take-Home Messages:
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Capillary refill time provides a valid, non-invasive resuscitation target that performs as well as lactate-guided protocols while potentially reducing fluid administration. This challenges the paradigm that biochemical markers are inherently superior to clinical assessment.
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Less fluid may be better: CRT-guided resuscitation achieved similar outcomes with reduced cumulative fluid balance, suggesting that peripheral perfusion assessment may facilitate more judicious fluid administration and earlier transition to vasopressor support.
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Clinical assessment retains value in the era of advanced monitoring: Standardized CRT assessment is accessible in resource-limited settings and does not require laboratory infrastructure or invasive monitoring.
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Personalized resuscitation targets may be preferable to universal protocols: The integration of multiple perfusion parameters (CRT, lactate, mental status, urine output) allows individualized decision-making rather than algorithmic rigidity.
Clinical Integration:
For intensive care trainees, ANDROMEDA-SHOCK-2 reinforces the importance of microcirculatory assessment and challenges reflexive approaches to fluid resuscitation. The trial validates bedside clinical skills and emphasizes that sophisticated monitoring does not necessarily improve outcomes compared to thoughtful physical examination.
Practical implementation requires training in standardized CRT assessment technique, including appropriate pressure application, timing, environmental control, and recognition of confounding factors (peripheral vascular disease, hypothermia, ambient temperature). Integration with other perfusion parameters creates a comprehensive assessment framework rather than reliance on isolated variables.
The finding that reduced fluid volumes achieved equivalent outcomes aligns with emerging evidence about fluid-related harm in critical illness. Clinicians should recognize that adequacy of resuscitation is determined by tissue perfusion rather than fluid volume administered. Early vasopressor initiation in patients with persistent hypoperfusion despite initial fluid boluses appears safe and may prevent fluid accumulation.
Trial 3: The DEMEL Trial - Melatonin for Delirium Prevention
Background and Rationale
Delirium represents one of the most common neuropsychiatric complications in critically ill patients, affecting up to 80% of mechanically ventilated ICU patients. The syndrome manifests as acute fluctuating disturbances in attention, awareness, and cognition, with profound implications for patient outcomes. Delirium independently predicts increased mortality, prolonged mechanical ventilation, extended ICU and hospital length of stay, long-term cognitive impairment, and reduced quality of life after discharge.
The pathophysiology of ICU delirium is multifactorial, involving neuroinflammation, neurotransmitter imbalances, oxidative stress, and circadian rhythm disruption. The ICU environment itself contributes through sensory overload, sleep deprivation, immobilization, and pharmacological exposures. Despite recognition of delirium as a critical care syndrome requiring attention, effective preventive and therapeutic interventions remain limited.
Melatonin, an endogenous neurohormone regulating circadian rhythms, has theoretical benefits in ICU delirium prevention through multiple mechanisms: circadian rhythm restoration, antioxidant effects, anti-inflammatory properties, and modulation of neurotransmitter systems. Observational data suggested promise, but definitive randomized controlled trial evidence was lacking.
Study Design and Methodology
The DEMEL trial represents the first large-scale randomized controlled investigation of melatonin for delirium prevention in critically ill patients. This multicenter, double-blind, placebo-controlled trial evaluated whether nightly melatonin administration could reduce delirium incidence in mechanically ventilated ICU patients.
Design Features:
- Double-blind, placebo-controlled randomized trial
- Enrollment of mechanically ventilated adults expected to require ICU care >48 hours
- Intervention: melatonin 10mg enterally each evening versus placebo
- Duration: throughout ICU admission or until hospital discharge
- Primary outcome: incidence of delirium assessed using validated CAM-ICU criteria
- Secondary outcomes: delirium duration, coma-free days, ventilator-free days, mortality, sleep quality assessments
Delirium assessment employed the Confusion Assessment Method for the ICU (CAM-ICU), performed systematically by trained personnel. Sleep quality was evaluated using actigraphy and subjective rating scales when patient interaction permitted. The trial maintained rigorous blinding through identical placebo preparations.
Key Findings
The DEMEL trial yielded disappointing results that challenge enthusiasm for melatonin as a delirium prevention strategy. Melatonin administration did not significantly reduce the incidence of delirium compared to placebo. Furthermore, secondary analyses revealed no meaningful differences in delirium duration, severity, or temporal patterns between groups.
Sleep quality assessments, while challenging to perform comprehensively in critically ill patients, did not demonstrate substantial improvements with melatonin therapy. Actigraphy data revealed persistent sleep fragmentation in both groups, suggesting that exogenous melatonin alone cannot overcome the multifactorial sleep disruption inherent to critical illness and the ICU environment.
Subgroup analyses exploring potential heterogeneity of treatment effect (age, illness severity, sedation exposure) did not identify populations deriving benefit from melatonin. The intervention was well-tolerated with no safety signals, but the absence of efficacy renders tolerability less clinically relevant.
Clinical Implications and Take-Home Messages
Primary Take-Home Messages:
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Melatonin does not effectively prevent delirium in critically ill patients, despite theoretical rationale and promising preliminary data. This underscores the complexity of delirium pathophysiology and the limitations of single-mechanism interventions.
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Circadian rhythm disruption cannot be addressed through pharmacological supplementation alone: The DEMEL trial suggests that restoring melatonin levels is insufficient when the fundamental ICU environment continues to disrupt normal sleep-wake cycles.
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Multicomponent delirium prevention strategies remain the standard of care: Pain management, sedation minimization, early mobilization, cognitive engagement, hearing/vision optimization, and sleep promotion through environmental modifications constitute evidence-based approaches.
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Negative trials provide valuable evidence: The DEMEL trial prevents widespread adoption of an ineffective intervention and redirects research efforts toward more promising strategies.
Clinical Integration:
For critical care trainees, the DEMEL trial provides important lessons about translating pathophysiological understanding into clinical interventions. Mechanistic plausibility does not guarantee therapeutic efficacy, and rigorous evaluation through adequately powered randomized trials remains essential before adopting new practices.
Delirium prevention requires systematic implementation of the ABCDEF bundle (Assess, prevent, and manage pain; Both spontaneous awakening and breathing trials; Choice of sedation and analgesia; Delirium monitoring and management; Early mobility; Family engagement). This multicomponent approach addresses multiple pathophysiological contributors rather than targeting single mechanisms.
The negative findings regarding melatonin do not negate the importance of sleep promotion in the ICU. Environmental modifications (noise reduction, lighting management, care clustering to minimize nighttime interruptions) and non-pharmacological sleep hygiene interventions remain rational components of comprehensive ICU care. Research should focus on novel approaches to sleep restoration and circadian rhythm alignment rather than simple supplementation strategies.
Trial 4: Balanced Crystalloids in Critical Care - Ongoing Evidence Synthesis
Background and Rationale
Intravenous fluid resuscitation represents one of the most ubiquitous interventions in critical care, yet fundamental questions about optimal fluid composition have generated substantial debate. Normal saline (0.9% sodium chloride) has historically dominated resuscitation practices based on availability, familiarity, and historical precedent rather than physiological rationale or robust comparative evidence.
Normal saline is supraphysiologic in chloride content (154 mEq/L versus 100 mEq/L in plasma), lacks buffer capacity, and contains no potassium or other electrolytes present in extracellular fluid. Large-volume saline administration predictably causes hyperchloremic metabolic acidosis and may contribute to acute kidney injury through renal vasoconstriction and inflammatory pathways. Balanced crystalloids (lactated Ringer's, Plasma-Lyte) more closely approximate physiological electrolyte composition and include buffer substrates.
Multiple observational studies and small randomized trials suggested potential benefits of balanced crystalloids, but definitive evidence from large pragmatic trials was limited. The SMART and SALT-ED trials demonstrated reduced major adverse kidney events with balanced crystalloids in non-critically ill patients, prompting investigation in ICU populations.
Study Design and Evolving Evidence
Multiple investigations in 2025 have continued to examine balanced crystalloid versus saline administration in critical care populations. Rather than a single definitive trial, the evidence base represents accumulating data from pragmatic cluster-randomized trials, registry studies, and meta-analyses synthesizing earlier investigations.
Recent Evidence Characteristics:
- Pragmatic cluster-randomized designs comparing ICU-wide balanced crystalloid versus saline protocols
- Inclusion of diverse critical care populations (septic shock, post-operative, medical ICU patients)
- Primary outcomes focused on acute kidney injury and mortality
- Secondary analyses exploring fluid balance, electrolyte disturbances, blood product utilization
These investigations build upon earlier trials by examining longer-term outcomes, exploring effect modification by illness severity and baseline renal function, and evaluating implementation challenges in real-world settings.
Key Findings and Emerging Consensus
The accumulated evidence increasingly favors balanced crystalloids for critically ill patients requiring significant fluid resuscitation. Meta-analyses incorporating recent trials demonstrate modest but consistent reductions in acute kidney injury incidence and need for renal replacement therapy with balanced crystalloid administration. The magnitude of benefit appears greatest in patients receiving larger resuscitation volumes and those with septic shock.
Mortality differences remain less definitive, with confidence intervals spanning no difference in many analyses. However, point estimates consistently favor balanced crystalloids, and the absence of harm combined with kidney protection provides compelling rationale for preferential use.
Hyperchloremic acidosis occurs less frequently with balanced crystalloids, though the clinical significance of avoiding this disturbance remains debated. Subgroup analyses suggest that patients with baseline acidosis or renal impairment may derive greater benefit from balanced fluid administration.
Cost considerations favor normal saline in many healthcare systems, though the price differential has narrowed as balanced crystalloid use has expanded. Economic analyses incorporating downstream costs of acute kidney injury (dialysis, prolonged hospitalization) suggest balanced crystalloids may be cost-effective despite higher acquisition costs.
Clinical Implications and Take-Home Messages
Primary Take-Home Messages:
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Balanced crystalloids should be the preferred resuscitation fluid for most critically ill patients, particularly those requiring large-volume resuscitation or at risk for acute kidney injury. The evidence supports clinical equipoise at minimum, with accumulating data favoring balanced solutions.
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Normal saline remains appropriate in specific clinical contexts: traumatic brain injury (avoidance of relative hypotonicity), hypochloremic alkalosis, and potentially hyponatremia. Clinician judgment should guide fluid selection based on individual patient physiology.
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The type of fluid matters, but the amount matters more: Avoiding excessive fluid administration provides greater outcome benefits than optimizing fluid composition. Balanced crystalloids do not mitigate harm from fluid overload.
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Implementation requires systems-level change: Transitioning from deeply ingrained normal saline practices necessitates institutional protocols, education, pharmacy support, and monitoring to ensure sustained practice change.
Clinical Integration:
For intensive care trainees, the balanced crystalloid evidence exemplifies how accumulating data gradually shifts practice patterns. Rather than a single transformative trial, progressive refinement of evidence quality eventually reaches a threshold supporting practice change.
Practical implementation involves establishing balanced crystalloids as default fluids in ICU order sets and automated dispensing systems. Education should emphasize the physiological rationale for balanced solutions while acknowledging clinical scenarios where normal saline remains preferable. Monitoring should track fluid composition, volumes administered, and outcomes (acute kidney injury, electrolyte disturbances) to ensure implementation success.
The crystalloid literature also illustrates the importance of asking the right clinical question. Early investigations compared crystalloids to colloids; contemporary research recognizes crystalloids as standard care and focuses on optimizing composition. Future research will likely examine more sophisticated questions about individualized fluid selection based on underlying pathophysiology, acid-base status, and inflammatory phenotypes.
Synthesis and Future Directions
The four trials examined in this review represent diverse aspects of critical care practice, yet several unifying themes emerge that should inform both clinical practice and future investigation.
Common Themes Across Trials
Precision and Personalization: Multiple trials demonstrate that universal protocols may be suboptimal compared to individualized approaches. ANDROMEDA-SHOCK-2 validates personalized resuscitation endpoints, while balanced crystalloid evidence suggests tailoring fluid composition to patient physiology. Future critical care medicine will likely emphasize phenotyping patients and matching interventions to biological characteristics rather than applying population-level protocols uniformly.
Multicomponent Interventions: The DEMEL trial's negative results underscore that complex syndromes like delirium cannot be addressed through single-mechanism interventions. Similarly, infection prevention requires comprehensive strategies beyond antimicrobial prophylaxis. Effective critical care increasingly involves orchestrating multiple simultaneous interventions rather than seeking singular therapeutic breakthroughs.
Pragmatic Trial Design: Several 2025 investigations employed pragmatic methodologies that enhance generalizability while accepting some loss of internal validity. Cluster-randomization, broad inclusion criteria, and flexible implementation strategies provide evidence more readily translated to diverse clinical settings than highly protocolized explanatory trials.
Systems and Implementation: The trials reviewed here require systems-level changes for successful adoption. SDD demands pharmacy infrastructure and monitoring capacity. CRT-guided resuscitation requires training and protocol integration. Balanced crystalloid use necessitates institutional commitment and order set modification. Evidence generation increasingly must consider implementation science alongside efficacy demonstration.
Implications for Critical Care Training
Postgraduate training programs must evolve to prepare intensivists for evidence-based practice in an era of rapid knowledge expansion:
Critical Appraisal Skills: Trainees must develop sophisticated abilities to evaluate trial design, statistical analyses, and applicability to their patient populations. Understanding concepts like pragmatic versus explanatory designs, cluster randomization, and effect modification becomes essential.
Physiological Reasoning: While trials guide practice, understanding underlying pathophysiology allows appropriate individualization. Knowing why balanced crystalloids theoretically benefit patients enables rational decision-making about when to deviate from standard protocols.
Implementation Science: Training should include exposure to quality improvement methodologies, practice guideline development, and strategies for translating evidence into sustained practice change. Intensivists increasingly serve as systems leaders responsible for protocol development and implementation.
Humility and Uncertainty: Negative trials like DEMEL and evolving controversies like fluid composition reinforce that critical care knowledge remains incomplete. Trainees should develop comfort with uncertainty and flexibility to modify practices as new evidence emerges.
Future Research Priorities
The 2025 trials illuminate areas requiring continued investigation:
Biomarker-Guided Therapy: Beyond lactate and CRT, novel biomarkers may enable more precise assessment of shock resolution, organ dysfunction, and therapeutic response. Multi-omic approaches could identify biological phenotypes that predict treatment response.
Antimicrobial Stewardship: While SDD demonstrates efficacy, questions persist about long-term resistance, alternative decontamination strategies, and optimal patient selection. Balancing infection prevention with antimicrobial resistance requires ongoing surveillance and adaptive protocols.
Neuropsychiatric Outcomes: Delirium prevention remains incompletely solved. Research should explore multicomponent interventions, early detection using advanced monitoring, and novel pharmacological approaches targeting neuroinflammation.
Fluid Optimization: Beyond crystalloid composition, questions remain about colloid use, restrictive versus liberal fluid strategies, de-resuscitation protocols, and individualized fluid responsiveness assessment.
Technology Integration: Artificial intelligence, continuous monitoring platforms, and decision support systems may enable more sophisticated integration of multiple data streams to guide therapeutic decisions.
Conclusion
The year 2025 has produced impactful evidence that should shape critical care practice for the coming years. The SuDDICU trial establishes selective digestive decontamination as an effective infection prevention strategy in appropriate contexts. ANDROMEDA-SHOCK-2 validates peripheral perfusion assessment as a resuscitation endpoint while challenging reflexive fluid administration. The DEMEL trial provides definitive negative evidence regarding melatonin for delirium prevention, redirecting efforts toward multicomponent strategies. Evolving balanced crystalloid evidence supports preferential use of physiological solutions for fluid resuscitation.
For postgraduate trainees in critical care, these trials exemplify the ongoing evolution of intensive care medicine through rigorous investigation. They demonstrate the value of questioning established practices, the importance of pragmatic trial designs, and the complexity of translating pathophysiological understanding into clinical benefit. Most importantly, they reinforce that critical care requires continuous learning, critical thinking, and adaptation as new evidence emerges.
The next generation of intensivists must embrace evidence-based practice while maintaining physiological reasoning, develop implementation skills alongside clinical expertise, and cultivate intellectual humility in the face of persistent uncertainty. The trials of 2025 provide a foundation for contemporary practice while illuminating the substantial work that remains to optimize outcomes for critically ill patients.
Key Take-Home Messages for Clinical Practice
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SuDDICU Trial: Selective digestive decontamination effectively reduces ICU-acquired infections without increasing antimicrobial resistance, with greatest benefit in units with higher baseline infection rates. Implementation requires comprehensive antimicrobial stewardship and ongoing surveillance.
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ANDROMEDA-SHOCK-2 Trial: Capillary refill time-guided resuscitation performs as well as lactate-guided protocols while potentially reducing fluid administration. Clinical assessment retains value alongside biochemical monitoring, and less fluid may achieve better outcomes than aggressive volume loading.
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DEMEL Trial: Melatonin does not prevent ICU delirium despite theoretical rationale. Multicomponent ABCDEF bundle implementation remains the evidence-based approach to delirium prevention, emphasizing pain control, sedation minimization, mobilization, and environmental optimization.
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Balanced Crystalloid Evidence: Physiological crystalloid solutions should be preferred over normal saline for most critically ill patients requiring resuscitation, with particular benefit for preventing acute kidney injury. However, fluid volume management supersedes composition in importance, and specific clinical scenarios may favor normal saline.
References
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Conflicts of Interest: None declared
Funding: None
For Postgraduate Medical Education Purposes
