Patient-Specific Adaptations in ERAS for High-Altitude Laparoscopic Cholecystectomy: The PAERS Hypothesis

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Abstract

Background

ERAS protocols reduce hospital stay by 1.88 days and complications by 29% globally, but their “one-size-fits-all” paradigm—validated at sea level—may fail at high altitude where chronic hypoxia and population-specific genetic adaptations remodel baseline physiology. No study has quantified ERAS effect weight shifts at high altitude or proposed a theoretical model to explain the gap.

Objectives

To evaluate three dimensions of plateau ERAS remodeling—(i) risk factor weight shift, (ii) traditional marker failure, (iii) genetic background modification—and propose the PAERS (Plateau Adaptation–ERAS Remodeling Syndrome) risk stratification model tailored to altitude.

Methods

Retrospective cohort of 612 adults undergoing elective laparoscopic cholecystectomy (2018–2023) at Qinghai Red Cross Hospital (2260 m). Three analytical tiers: (1) multivariable regression comparing risk factor coefficients against plain-altitude benchmarks; (2) restricted cubic spline and interaction modeling for Hb, SpO₂, and LOS; (3) inferential genetic modifier analysis using population-level EPAS1 carrier rates. Primary outcomes: LOS and complication rate.

Results

Three-dimensional shift was observed: (1) Weight Remodeling : BMI replaced sex as primary risk factor (OR = 1.86, P < .001), surgeon variability amplified (F = 6.33 vs plain benchmark 2–4, an ∼58% increase in F-statistic ratio, P < .001); (2) Marker Failure : Hb showed J-type relationship with LOS (Hb × SpO₂ interaction β = −0.0095, P = .009), with effect reversal across SpO₂ strata (”Plateau Hemoglobin Paradox”); (3) Genetic Modification (population-level inference) : ∼70% EPAS1 carrier rate (range 57–85% across studies) suggests HIF-2α pathway is a baseline modifier that must be accounted for. Three falsifiable predictions were proposed.

Conclusions

High-altitude ERAS faces three challenges: effect weight remodeling, biomarker failure, and genetic background calibration. The PAERS hypothesis proposes an integrated risk stratification model—shifting from “one-size-fits-all” to altitude-aware, patient-specific protocols.

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