Preprint Perioperative outcomes in myalgic encephalomyelitis/chronic fatigue syndrome undergoing general anesthesia…, 2026, Steinkirchner+

[SNT Gatchaman]

Perioperative outcomes in myalgic encephalomyelitis/chronic fatigue syndrome undergoing general anesthesia: a retrospective matched-pair study

Spoiler: Authors

Felix M Steinkirchner; Christina Kaufmann; Richard Felix Kraus; Maximilian Kaess; Elisabeth Schieffer; Bernhard M Graf; Christoph Lassen; Viktoria Kimmerling; Alexander Dejaco

BACKGROUND
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic multisystem disease characterized by profound fatigue, post-exertional malaise, cognitive impairment, and autonomic dysfunction. Its pathophysiology is incompletely understood and likely involves complex interactions between immune, autonomic, and metabolic dysregulation. Despite features with potential relevance for anesthesia and perioperative care, evidence to guide anesthetic management in individuals with ME/CFS remains limited. We therefore performed a retrospective matched-pair analysis to generate clinical data on perioperative responses and identify areas for future research.

METHODS
We conducted a retrospective matched-pair analysis at a single tertiary center. All patients with ME/CFS undergoing general anesthesia from 2015 to 2026 were identified using ICD-10 codes (G93.3 and U09.9) with additional manual verification and matched 1:1 to controls for comparison. Patients with confounding diagnoses or American Society of Anesthesiologists physical status above III were excluded. The analysis focused on intraoperative hemodynamic parameters, including baseline, post-induction, median, and lowest recorded systolic blood pressure and heart rate, as well as early postoperative outcomes in the post-anesthesia care unit (PACU), including maximum pain scores and requirement for rescue analgesia.

RESULTS
Out of 189 individuals identified through ICD-10 codes, 15 matched pairs were included after application of exclusion criteria. ME/CFS patients exhibited lower lowest recorded intraoperative systolic blood pressure (90 [82.5-95.0] mmHg in ME/CFS vs 100 [90.0-110.0] mmHg in controls, p = 0.044) as well as lower lowest heart rate (50 [40.0-57.5] bpm in ME/CFS vs 60 [50.0-65.0] bpm in controls, p = 0.012). Vasopressor use and fluid administration did not differ, and no episodes of severe hypotension or perioperative adverse events were observed. Postoperative pain was higher in ME/CFS, with higher maximum pain scores (NRS 5.0 [4.0-6.0] in ME/CFS vs 1.0 [0.0-4.0] in controls, p = 0.008) and more frequent opioid rescue analgesia (80% in ME/CFS vs 33% in controls, p = 0.039). Postoperative nausea or vomiting, oxygen supplementation, and PACU length of stay were similar between groups.

CONCLUSIONS
General anesthesia appears hemodynamically well tolerated in individuals with ME/CFS. In contrast, postoperative pain burden is increased and may require tailored analgesic strategies. Post-exertional malaise, a key disease feature with potentially delayed onset and significant impact, was not captured in this study and remains an important target for future research. These hypothesis-generating findings highlight the need for prospective studies to optimize perioperative management and evaluate patient-relevant outcomes in ME/CFS.

Web | DOI | PDF | Preprint: MedRxiv | Open Access

 

[Evergreen]

What a helpful study.

The "lower lowest recorded intraoperative systolic blood pressure" is interesting. I don't know about intraoperative, but each time I've had brief general anaesthesia, my blood pressure is low afterwards. There can be a bit of a hullabaloo about it in the recovery area. But by the time I get back to the ward, we have learned to just ask for the alarm to be turned off.

Sounds like it would be worth discussing pain options ahead of time.

 

[SNT Gatchaman]

Each eligible case with ME/CFS was matched 1:1 to a control subject without ME/CFS using two formal criteria: sex and surgical procedure (same or clinically comparable procedure). Additional variables were not used as formal matching criteria to avoid over-restriction of eligible pairs. Instead, relevant baseline and procedure related characteristics, including age, body mass index (BMI), anesthetic technique, and year of surgery, were assessed post hoc to evaluate comparability between groups.

ME/CFS represents a potentially vulnerable population that remains underrepresented in the anesthesia literature and for whom evidence-based perioperative guidance is currently lacking.

Intraoperatively, individuals with ME/CFS exhibited lower lowest intraoperative systolic blood pressure and heart rate values compared with matched controls. However, these differences did not translate into clinically relevant hemodynamic instability.

The observed hemodynamic differences may reflect underlying autonomic dysfunction, a common feature of ME/CFS.

In contrast, the increased postoperative pain burden may be related to altered nociceptive processing. Central sensitization has been documented in a substantial proportion of individuals with ME/CFS and may represent a plausible mechanism underlying the observed differences. Alternatively, pre-existing chronic pain or other unmeasured factors may have contributed, as preoperative pain scores were not available.

Crucially, post-exertional malaise - the hallmark feature of ME/CFS - typically manifests with delayed onset and is not captured by routine perioperative documentation focused on immediate outcomes. This has important implications not only for the assessment of anesthetic techniques and perioperative management strategies, but also for clinical practice, particularly in the context of repeated or staged interventions, where patients may undergo subsequent procedures while already in a state of post-exertional malaise. The increased postoperative pain and need for opioid analgesics in the ME/CFS cohort might be part of PEM.

the number of identified cases was substantially lower than expected based on population prevalence estimates, likely reflecting both underdiagnosis of ME/CFS and limitations of coding-based case identification, which may fail to capture diagnoses documented in clinical correspondence but not formally coded. Patients with ME/CFS may also avoid elective procedures due to concerns about post-exertional malaise, further contributing to underrepresentation. Consequently, the true perioperative burden of ME/CFS is likely underestimated.