A recent Intensive Care digest,
as sent to subscribers

Study Type: Single-centre retrospective observational cohort study

Key Question: What factors predict resumption of anticancer therapy and long-term survival after ICU discharge in patients with haematological malignancies?

Key Findings:

• Of 171 ICU survivors, 119 had further treatment indications; 89.1% resumed anticancer therapy despite significant functional decline during ICU stay (median performance status change -1.0, 95%CI -1.0 to -1.0).
• Cardiovascular disease reduced likelihood of treatment resumption (HR 0.41, 95%CI 0.20–0.84); malignancy diagnosed during ICU admission increased it (HR 3.03, 95%CI 1.53–6.01).
• Five-year survival was 36.1%; mortality risk was lower with infection as ICU admission cause (HR 0.54), new HM diagnosis during ICU stay (HR 0.31), and certain HM subtypes (HR 0.40).

Clinical Relevance: Supports pragmatic, disease- and comorbidity-informed ICU admission and treatment decisions for UK haemato-oncology patients, reassuring clinicians that ICU survival does not preclude continued cancer treatment.

Limitations: Single-centre retrospective design limits generalisability and introduces potential selection and confounding bias.

Study Type: Double-blind randomized controlled trial (single-centre, with post hoc per-protocol analysis)

Key Question: Does indirect calorimetry (IC)-guided nutrition improve weaning success and time to liberation from prolonged mechanical ventilation compared with predictive-equation-guided feeding?

Key Findings:

• Successful weaning occurred in 58% (IC) vs 50% (control); median time to weaning 27 vs 31 days—neither difference statistically significant (p=0.33 and p=0.58).
• One-year mortality was numerically lower with IC (48% vs 56%; absolute difference -8%, 95% CI -21.2 to 5.5%, p=0.29).
• Smaller "energy-gap" (measured expenditure vs delivered intake) independently predicted successful weaning (HR 1.02 per 50 kcal/day reduction, p=0.02); successful weaning independently reduced 1-year mortality (HR 0.54, 95% CI 0.36–0.82).

Clinical Relevance: Supports growing interest in metabolically-guided feeding for long-stay ventilated patients in UK critical care/rehabilitation units, though current evidence does not yet justify routine IC adoption over standard predictive equations.

Limitations: Single-centre design and underpowered sample size limit definitive conclusions; findings are hypothesis-generating pending larger multicentre trials.

Study Type: Narrative review

Key Question: What role does NLRP3 inflammasome activation play in sepsis and critical illness, and how might this be therapeutically targeted?

Key Findings:

• NLRP3 activation drives caspase-1-dependent IL-1β/IL-18 maturation and pyroptosis; excessive activation is linked to hyperinflammation, endothelial dysfunction, immunothrombosis, and multi-organ failure in sepsis/ARDS.
• Conversely, exhausted or insufficient inflammasome responses may impair pathogen clearance and increase risk of secondary infection, indicating a biphasic, time-dependent role.
• IL-1 blockade (e.g., anakinra) and upstream pathway inhibitors are proposed immunomodulatory strategies, but no definitive clinical efficacy data are presented in this review.

Clinical Relevance: Understanding the dual protective/pathogenic role of NLRP3 signalling may inform future biomarker-guided immunomodulatory therapies for sepsis and ARDS relevant to UK critical care practice, where phenotype-targeted treatment remains an unmet need.

Limitations: As a narrative review, it synthesises mechanistic and preclinical evidence without systematic methodology or robust clinical trial data supporting translation.

Study Type: Narrative review

Key Question: How does therapeutic plasma exchange (TPE) affect the pharmacokinetics and dosing of anti-infective drugs in critically ill patients?

Key Findings:

• TPE typically exchanges 1.0–1.5 plasma volumes over 90–140 minutes, but this varies considerably in practice.
• Drugs with low volume of distribution and high protein binding (e.g., aminoglycosides, glycopeptides) are most susceptible to significant removal during TPE.
• Direct pharmacokinetic evidence for anti-infectives during TPE in sepsis is limited, and no validated dosing/timing algorithms currently exist.

Clinical Relevance: With two multicentre trials evaluating TPE in early septic shock and TPE increasingly used in UK critical care for multiple indications, clinicians must anticipate potential subtherapeutic anti-infective levels and consider individualised dose adjustment or therapeutic drug monitoring around TPE sessions.

Limitations: As a narrative (non-systematic) review, it synthesises heterogeneous, largely low-quality pharmacokinetic data without formal quality appraisal, limiting the strength of practical dosing recommendations.

Study Type: Secondary analysis of an RCT (PEPaNIC trial)

Key Question: Does increased ureagenesis (urea/urea-creatinine ratio) explain the harm associated with early parenteral nutrition (PN) in critically ill children?

Key Findings:

• Early-PN patients had persistently higher urea and urea/creatinine ratio (UCR) than late-PN patients over the first 11 PICU days.
• Higher week-1 maximum UCR independently predicted new infection (aOR 1.75, 95%CI 1.35–2.27), delayed PICU discharge (aHR 0.75, 0.67–0.82) and hospital discharge (aHR 0.78, 0.70–0.86), and increased 90-day mortality (aOR 1.43, 1.03–1.99), statistically mediating part of the harm from early-PN.
• Similar associations held for absolute urea concentrations.

Clinical Relevance: Supports UK PICU practice of withholding early PN and suggests urea/UCR could become a bedside biomarker to individualise nutrition timing and dosing in critically ill children.

Limitations: This is an observational, hypothesis-generating secondary analysis showing statistical mediation, not proven causation, and requires prospective validation before clinical implementation.

Study Type: Retrospective population-based cohort study

Key Question: Does the choice of antipsychotic (haloperidol or risperidone vs quetiapine) prescribed after TBI hospitalisation affect the risk of post-traumatic epilepsy in older adults?

Key Findings:

• Among 1204 TBI survivors (age ≥66) prescribed antipsychotics post-discharge, epilepsy occurred in 6% (haloperidol), 13% (risperidone), and 14% (quetiapine).
• No significant difference in adjusted epilepsy risk versus quetiapine: haloperidol aHR 0.73 (95% CI 0.39–1.34); risperidone aHR 0.94 (95% CI 0.65–1.36).
• Five-year mortality was markedly higher with haloperidol (89%) than risperidone (66%) or quetiapine (62%), suggesting confounding by indication/frailty.

Clinical Relevance: For UK ICU/critical care clinicians managing agitation or delirium after TBI, this study offers reassurance that antipsychotic choice does not appear to meaningfully alter post-traumatic epilepsy risk, though drug selection should still consider sedation profile, cardiac risk, and mortality-associated confounders.

Limitations: Very high and differential mortality across groups, plus wide confidence intervals, limits comparability and statistical power, warranting cautious interpretation pending confirmatory studies.

Study Type: Phase 2 multicentre randomised, double-blinded, placebo-controlled trial

Key Question: Does perioperative ilofotase alfa reduce postoperative renal functional impairment in patients at high risk of acute kidney injury after on-pump cardiac surgery?

Key Findings:

• No significant difference in peak serum creatinine ratio: 1.21±0.42 (ilofotase alfa) vs 1.27±0.50 (placebo), p=0.31.
• MAKE60 incidence similar between groups: 15.9% vs 15.4% (p=0.87).
• No safety concerns identified with ilofotase alfa administration.

Clinical Relevance: Cardiac surgery-associated AKI remains a common, morbidity-driving complication in NHS cardiothoracic ICUs, but this trial indicates ilofotase alfa offers no renoprotective benefit, tempering enthusiasm for its adoption pending further evidence.

Limitations: Phase 2 design with modest sample size (n=204) may be underpowered to detect smaller but clinically meaningful treatment effects.

Study Type: Cross-sectional observational study

Key Question: Does peripheral perfusion (capillary refill time [CRT], perfusion index [PI]) reliably reflect sublingual and nailfold microcirculatory status in septic shock?

Key Findings:

• Septic shock patients (n=29) showed marked sublingual/nailfold microcirculatory derangement, prolonged CRT, and reduced PI versus healthy volunteers (n=34).
• CRT correlated with flow-related microcirculatory parameters but not with perfused vascular density (a diffusion-related parameter); nailfold microcirculation showed no association with either CRT or PI.
• A subset of patients with normal CRT still had abnormal sublingual microcirculation; ROC analysis showed CRT had limited diagnostic accuracy for detecting microcirculatory alteration.

Clinical Relevance: For UK intensive care clinicians relying on CRT as a simple, bedside resuscitation target, these findings caution that a normal CRT does not exclude ongoing microcirculatory dysfunction, particularly diffusion-related impairment relevant to tissue oxygenation.

Limitations: Small single-timepoint sample without longitudinal or outcome data limits generalisability and causal inference regarding resuscitation guidance.