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Daily Report

Daily Anesthesiology Research Analysis

01/24/2025
3 papers selected
3 analyzed

Three studies advance anesthesiology and perioperative science: (1) a porcine model shows that short periods of underassisted ventilation exacerbate preexisting ventilator-induced diaphragm dysfunction with structural injury; (2) a mechanistic study reveals that sprouting sympathetic fibers co-release norepinephrine and CXCL16 in dorsal root ganglia to drive neuropathic pain; and (3) a systematic review/meta-analysis finds that subjectively assessed functional capacity <4 METs strongly predicts

Summary

Three studies advance anesthesiology and perioperative science: (1) a porcine model shows that short periods of underassisted ventilation exacerbate preexisting ventilator-induced diaphragm dysfunction with structural injury; (2) a mechanistic study reveals that sprouting sympathetic fibers co-release norepinephrine and CXCL16 in dorsal root ganglia to drive neuropathic pain; and (3) a systematic review/meta-analysis finds that subjectively assessed functional capacity <4 METs strongly predicts postoperative cardiovascular events and complications.

Research Themes

  • Ventilation strategy and diaphragm injury in critical care
  • Neuroimmune mechanisms of neuropathic pain
  • Preoperative risk stratification using subjective functional capacity

Selected Articles

1. Sprouting sympathetic fibres release CXCL16 and norepinephrine to synergistically mediate sensory neuronal hyperexcitability in a rodent model of neuropathic pain.

82.5Level VBasic/Mechanistic research (rodent models)
British journal of anaesthesia · 2025PMID: 39848871

In rodent spared nerve injury models, sprouting sympathetic fibers in the dorsal root ganglia maintained mechanical allodynia. These fibers co-released norepinephrine and the chemokine CXCL16, which synergistically increased sensory neuronal excitability, revealing a neuroimmune mechanism for neuropathic pain maintenance.

Impact: This is among the first demonstrations that sympathetic sprouting drives neuropathic pain via co-release of a chemokine (CXCL16) and norepinephrine, opening therapeutic avenues beyond conventional analgesics.

Clinical Implications: Targeting CXCL16 signaling and/or sympathetic activity (e.g., chemokine blockade, adrenergic modulation, sympathectomy) may provide new strategies for refractory neuropathic pain, with implications for perioperative and chronic pain management.

Key Findings

  • Sprouting tyrosine hydroxylase-positive sympathetic fibers in DRG maintained mechanical allodynia after SNI.
  • Sympathetic terminals co-released norepinephrine and CXCL16, synergistically increasing sensory neuron excitability.
  • Lumbar sympathectomy and targeted DRG manipulations modulated pain behaviors, supporting a causal role of sympathetic-sensory interactions.

Methodological Strengths

  • Multimodal mechanistic approach (sympathectomy, DRG viral/pharmacologic interventions, MeRIP-seq, RNA-seq, immuno-EM).
  • Behavioral assays coupled with cellular/molecular readouts in validated neuropathic pain models.

Limitations

  • Rodent models may not fully recapitulate human neuropathic pain complexity.
  • Dose-response and temporal dynamics of CXCL16/norepinephrine co-release in vivo require further quantification.

Future Directions: Validate CXCL16-adrenergic co-signaling in human tissues; test CXCL16 blockade or combined adrenergic modulation in translational models; and explore biomarkers for patient stratification.

BACKGROUND: Chronic neuropathic pain generally has a poor response to treatment with conventional drugs. Sympathectomy can alleviate neuropathic pain in some patients, suggesting that abnormal sympathetic-somatosensory signaling interactions might underlie some forms of neuropathic pain. The molecular mechanisms underlying sympathetic-somatosensory interactions in neuropathic pain remain obscure. METHODS: Lumbar sympathectomy was performed in spared nerve injury (SNI) mice or rats, and the up-down method was used to measure the mechanical paw withdrawal threshold. Dorsal root ganglia (DRG) injection and perfusion were used to deliver virus or drugs. Methylated RNA immunoprecipitation sequencing, RNA-sequencing, and immunoelectron microscopy were used to identify neurotransmitters. RESULTS: We found that sprouting tyrosine hydroxylase-positive sympathetic fibres in DRG mediated the maintenance of mechanical allodynia after SNI (day 28, P<0.001). We further found that SNI significantly increased the N

2. Impact of Underassisted Ventilation on Diaphragm Function and Structure in a Porcine Model.

71Level VBasic/Mechanistic research (large animal)
Anesthesiology · 2025PMID: 39854688

In piglets with preexisting VIDD, just 2 hours of underassisted ventilation further reduced diaphragm pressure-generating capacity by 29% and increased sarcomeric injuries, while no-VIDD animals maintained function. These findings indicate that underassistance can rapidly worsen diaphragm dysfunction and structural injury when VIDD is present.

Impact: This directly informs weaning and assisted ventilation strategies by demonstrating harm from underassistance in the context of VIDD, a prevalent ICU condition.

Clinical Implications: Avoid aggressive unloading that results in underassistance in patients with suspected VIDD; monitor diaphragm function where feasible; and individualize assisted ventilation to maintain adequate diaphragmatic effort.

Key Findings

  • In VIDD piglets, diaphragm pressure-generating capacity fell 29% after 2 hours of underassisted ventilation.
  • Underassisted ventilation increased sarcomeric injury area (13% to 24%) and decreased lipid droplets in VIDD animals.
  • No significant functional decline occurred in the no-VIDD group during underassisted ventilation.

Methodological Strengths

  • Transvenous phrenic nerve stimulation provided objective supramaximal diaphragm function measures.
  • In vivo mini-invasive biopsies enabled paired structural assessment before/after intervention.

Limitations

  • Animal model; clinical translation requires human validation.
  • Short underassistance exposure (2 h) limits inference on longer durations and recovery.

Future Directions: Prospective human studies to define safe assisted effort targets in suspected VIDD; evaluate diaphragm-protective weaning protocols and monitoring (e.g., diaphragmatic ultrasound or pressure-time product).

BACKGROUND: Long-term controlled mechanical ventilation in the intensive care unit induces ventilator-induced diaphragm dysfunction (VIDD). The transition from controlled mechanical ventilation to assisted mechanical ventilation is a challenge that requires clinicians to balance overassistance and underassistance. While the effects of overassistance on the diaphragm are well known, the authors aimed to assess the impact of underassistance on diaphragm function and structure in a piglet model with preexisting VIDD (after long-term controlled mechanical ventilation) or without VIDD (short-term controlled mechanical ventilation). METHODS: Twenty-two Large White female piglets were anesthetized, ventilated, and separated into two groups: a VIDD group (n = 10) with long-term 72-h controlled mechanical ventilation, and a no-VIDD group (n = 12) with short-term 2-h controlled mechanical ventilation. After sedation reduction at the end of the controlled mechanical ventilation period, each piglet was switched to underassisted ventilation for 2 h. Diaphragm function (supramaximal diaphragm pressure-generating capacity assessed by negative tracheal pressure after transvenous phrenic nerve stimulation) and diaphragm structure (mini-invasive in vivo biopsies) were assessed before and after underassisted ventilation. RESULTS: In the VIDD group, supramaximal diaphragm pressure-generating capacity decreased by 22% from (mean ± SD) 69.9 ± 12.7 to 54.9 ± 19.7 cm H 2 O ( P = 0.04) after 72 h of controlled mechanical ventilation evidencing VIDD, then dropped by a further 29% from 54.9 ± 19.7 to 38.9 ± 15.5 cm H 2 O ( P < 0.01) after 2 h of underassisted ventilation. Diaphragm pressure-generating capacity remains stable from 55.3 ± 22.7 to 58.2 ± 24 cm H 2 O ( P = 0.24) in the no-VIDD group. Diaphragm structure showed that sarcomeric injuries increase from 13 ± 10% to 24 ± 19% ( P < 0.01) and lipid droplets decrease from 14 ± 8% to 11 ± 6% ( P = 0.03) of the total micrograph area after 2 h of underassisted ventilation in the VIDD group. Sarcomeric injuries and lipid droplets accounted, respectively, for 17 ± 16% and 2 ± 3% of the total micrograph area after underassisted ventilation in the no-VIDD group. CONCLUSIONS: In this porcine model, a short 2-h exposure of underassisted ventilation induces impairment of diaphragm function with damage to the diaphragm structure in intensive care unit condition with preexisting VIDD.

3. Pre-operative subjective functional capacity and postoperative outcomes in adult non-cardiac surgery: a systematic review and meta-analysis.

68.5Level ISystematic Review/Meta-analysis
Anaesthesia · 2025PMID: 39853751

Across 23 studies, patients reporting subjective functional capacity <4 METs had significantly higher odds of postoperative MACE (OR 1.84), mortality (OR 2.48), and complications (OR 1.85). Multiple assessment approaches converged on similar risk stratification despite heterogeneity.

Impact: This synthesis supports practical use of simple subjective functional assessments to identify high-risk patients when objective testing is unavailable or infeasible.

Clinical Implications: Incorporate a threshold of <4 METs from subjective assessment to trigger enhanced perioperative optimization, cardiopulmonary evaluation, and monitoring; consider prehabilitation and risk-informed anesthesia planning.

Key Findings

  • Subjective functional capacity <4 METs was associated with higher postoperative MACE (OR 1.84).
  • Poor functional capacity predicted higher mortality (OR 2.48) and overall complications (OR 1.85).
  • Findings were consistent across questionnaires, specific questions, and anesthetist subjective assessments.

Methodological Strengths

  • Comprehensive search across four databases with random-effects meta-analysis.
  • Consistent effect sizes across varied subjective assessment methods.

Limitations

  • Heterogeneity in functional capacity assessment tools and outcome definitions.
  • Observational nature of included studies limits causal inference.

Future Directions: Prospective studies standardizing subjective functional capacity instruments; head-to-head comparisons with objective measures; and integration into perioperative risk calculators.

INTRODUCTION: Assessment of functional capacity is an essential part of peri-operative risk stratification. Subjective functional capacity is easier to examine than objective tests of patient fitness. However, the association between subjective functional capacity and postoperative outcomes has not been established. METHODS: Four databases were searched for studies describing the associations between subjective functional capacity and postoperative outcomes in adults undergoing non-cardiac surgery. Meta-analysis was conducted among studies where functional capacity was expressed in metabolic equivalents. The primary outcome was postoperative major adverse cardiovascular events. Secondary outcomes were mortality and postoperative overall complications. We estimated the ORs of the outcomes in patients with poor functional capacity (< 4 metabolic equivalents) as compared with those with good functional capacity (≥ 4 metabolic equivalents). Random-effects models were used for the meta-analysis. RESULTS: We identified 7835 abstracts. After screening and a full-text review, 23 studies were selected. Evaluation methods of functional capacity included: questionnaires (n = 7); specific questions (n = 6); and subjective assessment by anaesthetists (n = 5). The probability of major postoperative adverse cardiovascular events was significantly higher in patients with poor functional capacity (OR 1.84, 95%CI 1.62-2.08) than in those with good functional capacity. Patients with poor functional capacity also had higher odds of mortality (OR 2.48, 95%CI 1.45-4.25) and postoperative complications (OR 1.85, 95%CI 1.34-2.55). DISCUSSION: Subjective functional capacity of < 4 metabolic equivalents was associated with postoperative complications including cardiovascular events and other serious outcomes. The results need to be interpreted with caution due to the diverse measures used to assess functional capacity.