BACKGROUND:Prehabilitation is an emerging preoperative strategy designed to optimize patients' functional capacity before surgery to improve postoperative outcomes. Previous studies have demonstrated its clinical benefit, including enhanced recovery and reduced postoperative complications. However, the mechanisms underlying these benefits remain poorly understood. The aim of this exploratory study was to investigate the potential effects of prehabilitation on preoperative and postoperative immune function. METHODS:This prospective study utilized data and material from a subgroup of patients participating in the F4S PREHAB trial (NL73777.091.20), which is a stepped-wedge trial investigating the effects of multimodal prehabilitation before major surgery. In this substudy, patients who underwent elective bladder, oesophageal, or rectal cancer surgery between June 2022 and November 2023 were included. Immune function was assessed at baseline, after the prehabilitation or usual care interval, and on postoperative day 1 (POD1) by examining ex vivo cytokine production capacity, plasma cytokine concentrations, and monocytic human leucocyte antigen DR (mHLA-DR) expression. RESULTS:This substudy included 130 patients: 102 in the prehabilitation group and 28 in the control group. After prehabilitation, the ex vivo production of pro-inflammatory cytokines was reduced, whereas the ex vivo production of the anti-inflammatory cytokine interleukin 10 (IL-10) was increased. Plasma concentrations of interleukin 6 (IL-6) and IL-10 were lower after prehabilitation. On POD1, no significant differences in postoperative immune function were observed between the prehabilitation and control groups. CONCLUSION:This study suggests that multimodal prehabilitation influences basal immune function, leading to a less inflammatory state. However, as no significant differences in immune function were observed between the prehabilitation and control groups on POD1, the impact of prehabilitation on postoperative immune function may be limited.

Background and Objectives: Gastrointestinal (GI) endoscopy requires safe and effective sedation. Remimazolam, an ultra-short-acting benzodiazepine, may offer advantages over traditional sedatives like midazolam and propofol, including rapid onset, short half-life, and a favorable safety profile. This study evaluates the feasibility, safety, and patient satisfaction of continuous remimazolam infusion administered by trained gastroenterologists for GI endoscopy. Materials and Methods: This prospective registry included patients with ASA physical status I and II undergoing standard endoscopic procedures. Continuous remimazolam sedation was administered, with boluses given as needed. Vital signs were monitored, and patient satisfaction was assessed before and after the procedure using standardized questionnaires. Results: A total of 159 procedures were performed in 141 patients. Sedation was successful in all patients, with a mean induction dose of 7.1 mg and total infusion of 15.1 mg. Recovery time averaged 3.3 min. Adverse events, including transient hypotension and hypoxia, occurred in 11.3% of patients but were easily managed. Most patients (97%) reported sufficient comfort, with an average satisfaction score of 8.1/10. Conclusions: Continuous remimazolam infusion administered by trained gastroenterologists is a safe and effective alternative to traditional propofol sedation for GI endoscopy. It offers stable sedation, rapid recovery and high patient satisfaction, potentially reducing anesthesiology workload and improving procedural efficiency. Further studies are needed to confirm these findings in broader patient populations.

BACKGROUND:Major surgery elicits a complex immune response involving both systemic inflammation and innate immune suppression. These changes may contribute to postoperative infectious complications. This study aimed to determine whether perioperative immune activation and suppression patterns are associated with the development of postoperative infectious complications. MATERIALS AND METHODS:A pooled analysis of six prospective clinical studies was conducted to evaluate perioperative immune function in patients undergoing diverse surgical procedures. Immune monitoring included plasma danger-associated molecular pattern and cytokine concentrations, ex vivo cytokine production after lipopolysaccharide stimulation of whole blood, and proteomic profiling. Clinical outcomes included postoperative infections, pain scores, and quality of recovery. RESULTS:A total of 487 patients were included. Danger-associated molecular patterns generally increased following surgery. All surgical procedures induced a stereotypical immune trajectory, characterized by early plasma interleukin (IL)-6 and IL-10 elevation and suppression of ex vivo tumor necrosis factor (TNF) and IL-1β production, most pronounced on postoperative day 1. Immune suppression persisted through POD3 in patients undergoing colorectal surgery, but resolved more quickly after breast surgery, a less invasive procedure. Patients who developed post-operative infections had higher plasma IL-6 and TNF concentrations on postoperative day 1 and attenuated ex vivo TNF production on postoperative day 3. Proteomic profiling confirmed IL-6 upregulation and identified consistent downregulation of multiple immune signaling proteins, including IFN-γ and chemokines involved in lymphocyte activation. CONCLUSION:Surgical injury initiates a coordinated immune response with early inflammation and delayed innate immune suppression. Failure to recover innate immune function by postoperative day 3 is associated with increased infection risk. Perioperative immune profiling may enable early risk stratification and inform targeted immunomodulatory strategies.

Hypercapnic hyperventilation is a technique used to support emergence from volatile anesthesia by allowing a controlled elevation of arterial carbon dioxide (CO₂) levels. The resulting hypercapnia increases minute ventilation, enhances the washout of anesthetic gases from the lungs, and increases cerebral blood flow, which may facilitate faster elimination of volatile agents from brain tissue. Commercial devices have been developed to achieve this effect; however, their availability is limited in many regions. This protocol describes a practical alternative approach using standard anesthesia equipment commonly available in European hospitals. By temporarily removing the CO₂ absorber and reducing fresh gas flow, controlled CO₂ rebreathing is facilitated, while an active charcoal filter eliminates residual volatile anesthetics from the circuit. The protocol provides step-by-step guidance to help achieve the desired end-tidal CO₂ levels safely and efficiently. This method offers a practical and low-cost way to induce hypercapnic hyperventilation, which may be associated with faster emergence from anesthesia under appropriate clinical conditions.

Postoperative pain remains a common clinical challenge, affecting patient recovery, satisfaction, and risk of chronic pain. Conventional analgesics often inadequately address the multifactorial nature of postoperative pain, while opioids carry risks of adverse effects and dependence. Multimodal analgesia, combining agents with complementary mechanisms, aims to improve pain control and reduce opioid consumption, but the incremental benefit of adding a second component is unclear. To evaluate whether adding a second multimodal analgesic component to conventional regimens improves postoperative pain control and reduces opioid consumption in adult patients undergoing non-cardiac surgery. We performed a systematic review and meta-analysis of randomized controlled trials. PubMed and EMBASE (via Ovid) were searched for eligible studies up to August 2, 2024, using search terms related to surgical patients, pain, multimodal analgesia, and ten common multimodal components. We included RCTs in adults (≥ 18 years) undergoing non-cardiac surgery under general anesthesia, comparing standard care plus two multimodal components versus one component, with postoperative opioid consumption measured and pain measured by numeric rating scale (NRS) or visual analog scale (VAS). Twenty-seven trials were included. Meta-analysis of 17 trials (24 comparisons) showed that a second multimodal component reduces 24-hour opioid consumption by 5.2 mg oral morphine equivalents (95

Background:Recently, the minimally invasive transcervical esophagectomy (MICE) technique was introduced as a new approach for esophagectomy. The aim of this explorative study was to compare the effects of minimally invasive transthoracic esophagectomy (MIE), the most commonly used esophagectomy technique, versus MICE on postoperative immune function. Methods:For this explorative cohort study, data regarding 42 F4S PREHAB trial participants (NL8699, International Clinical Trials Registry Platform) were analyzed. Immune function was assessed preoperatively and on postoperative day 1 (POD1) via plasma cytokines [interleukin (IL)-6, tumor necrosis factor (TNF), and IL-10], damage-associated molecular patterns (DAMPs) (S100A8/A9 and S100A12), and the Olink targeted proteomics inflammation panel. Ex vivo cytokine production was measured using whole blood stimulation with Escherichia coli lipopolysaccharides. Circulating C-reactive protein (CRP) concentrations (end of surgery until POD7) were analyzed in the F4S PREHAB cohort, supplemented with additional patients who underwent MICE or MIE in the same hospital. Results:Concentrations of circulating cytokines and DAMPs, ex vivo cytokine production, and levels of additional inflammatory proteins on POD1 did not differ between groups (MIE, n=21; MICE, n=21). The dynamics of circulating CRP concentrations during the first week after surgery were also similar in the MICE (n=61) and MIE (n=66) groups. Conclusions:This explorative study found no differences in postoperative inflammatory status between the two procedures. Limited statistical power and sample size warrant larger trials to further investigate potential differences in postoperative immune response and clinically relevant outcomes.

Increasing evidence shows that postoperative innate immune dysregulation is associated with delayed recovery and infectious complications. The aim of this study was to compare the effects of general versus spinal anesthesia on innate immune function during and after total hip arthroplasty (THA). This comparative matched cohort study used data from two single-center randomized-controlled trials. Patients from the control group of the HIPPO study received general anesthesia and were matched to control patients from the MAGIC study who received spinal anesthesia in a 2:1 ratio (general(n = 18); spinal(n = 9)). Immune function was assessed by determination of ex vivo cytokine production capacity upon whole blood stimulation with E. coli lipopolysaccharides (LPS) and measurement of plasma cytokines and danger-associated molecular patterns (DAMPs). In the general anesthesia group, ex vivo cytokine production capacity of IL-1β was significantly lower shortly after induction (p = 0.02) and both IL-1β and IL-6 were significantly lower at the end of surgery compared to the spinal anesthesia group (p = 0.002 and p = 0.02, respectively). On postoperative day 1 (POD1), no differences were observed. Plasma cytokine concentrations did not differ between the spinal and general anesthesia group at most timepoints, except for IL-10 at the end of surgery (p = 0.04) and TNF on POD1 (p = 0.04), which were higher in the general anesthesia group. Plasma concentrations of DAMPs did not differ between the groups. General anesthesia has a transient impact on innate immune function in patients undergoing THA, but the clinical significance of anesthesia-induced innate immune dysregulation might be limited as no differences were observed on POD1. The HIPPO study (NCT05562999, date of registration 2022-10-03) and MAGIC study (NCT05723406, date of registration 2023-02-10) are registered at ClinicalTrials.gov.

Introduction: Difficult airway management is a critical challenge in anesthesia, often necessitating advanced techniques to ensure patient safety. A patient presented with a malignant lesion on the epiglottis, significantly altering the airway anatomy. Flexible rhinolaryngoscopy revealed a laryngeal carcinoma affecting the entire epiglottis, causing thickening and displacement, which suggested the potential for difficult intubation. Methods: Given the expected feasibility of bag-mask ventilation and front-of-neck access, an asleep intubation technique was selected. The combined use of a McGrath video laryngoscope and C-MAC video stylet allowed for fast and easy atraumatic intubation on the first attempt. The anesthetic and surgical course was uneventful. Discussion: This case report highlights the successful use of a combined approach involving a video laryngoscope and video stylet for intubation in a patient with known difficulties in airway management, providing insights into the benefits of enhanced visualization and maneuverability. The rigid design and steerable tip of the C-MAC video stylet provide advantages over traditional flexible optics, offering better maneuverability and reducing the need for a second operator. Although this technique was successful in this case, its use in patients with complex airway pathologies warrants careful preoperative assessment and collaboration with an experienced airway management team.

BACKGROUND:Colorectal surgery is associated with moderate-to-severe postoperative complications in over 25% of patients, predominantly infections. Monocyte epigenetic alterations leading to immune tolerance could explain postoperative increased susceptibility to infections. This research explores whether changes in monocyte DNA accessibility contribute to postoperative innate immune dysregulation. METHODS:Damage-associated molecular patterns (DAMPs) and ex vivo cytokine production capacity were measured in a randomized controlled trial (n = 100) in colorectal surgery patients, with additional exploratory subgroup proteomic (proximity extension assay; Olink) and epigenomic analyses (Assay for Transposase-Accessible Chromatin [ATAC sequencing]). Monocytes of healthy volunteers were used to study the effect of high-mobility group box 1 (HMGB1) and heat shock protein 70 (HSP70) on cytokine production capacity in vitro. RESULTS:Plasma DAMPs were increased after surgery. HMGB1 showed a mean 235% increase from before- (preop) to the end of surgery (95% confidence interval [CI] [166 - 305], P < .0001) and 90% increase (95% CI [63-118], P = .0004) preop to postoperative day 1 (POD1). HSP70 increased by a mean 12% from preop to the end of surgery (95% CI [3-21], not significant) and 30% to POD1 (95% CI [18-41], P < .0001). Nuclear deoxyribonucleic acid (nDNA) increases by 66% (95% CI [40-92], P < .0001) at the end of surgery and 94% on POD1 (95% CI [60-127], P < .0001). Mitochondrial DNA (mtDNA) increases by 370% at the end of surgery (95% CI [225-515], P < .0001) and by 503% on POD1 (95% CI [332-673], P < .0001). In vitro incubation of monocytes with HSP70 decreased cytokine production capacity of tumor necrosis factor (TNF) by 46% (95% CI [29-64], P < .0001), IL-6 by 22% (95% CI [12-32], P = .0004) and IL-10 by 19% (95% CI [12-26], P = .0015). In vitro incubation with HMGB1 decreased cytokine production capacity of TNF by 34% (95% CI [3-65], P = .0003), interleukin 1β (IL-1β) by 24% (95% CI [16-32], P < .0001), and IL-10 by 40% (95% CI [21-58], P = .0009). Analysis of the inflammatory proteome alongside epigenetic shifts in monocytes indicated significant changes in gene accessibility, particularly in inflammatory markers such as CXCL8 (IL-8), IL-6, and interferon-gamma (IFN-γ). A significant enrichment of interferon regulatory factors (IRFs) was found in loci exhibiting decreased accessibility, whereas enrichment of activating protein-1 (AP-1) family motifs was found in loci with increased accessibility. CONCLUSIONS:These findings illuminate the complex epigenetic modulation influencing monocytes' response to surgical stress, shedding light on potential biomarkers for immune dysregulation. Our results advocate for further research into the role of anesthesia in these molecular pathways and the development of personalized interventions to mitigate immune dysfunction after surgery.

There is an ongoing quest for an ideal uniform anesthesia regimen that adequately covers all nociceptive stimuli preventing hypertension and tachycardia while minimizing hypotension and the need for antihypotensive drugs. Recently, the ultra-short-acting benzodiazepine remimazolam was approved for the induction and maintenance of general anesthesia. Combining remimazolam with sevoflurane and propofol may combine the antiemetic properties of propofol, the depressing (immobilizing) effect on spinal motor neurons of sevoflurane, and the hemodynamic stability afforded by remimazolam, making it an attractive addition to the armamentarium of anesthetic agents. We describe five patients in whom general anesthesia was maintained with this triple combination, along with multimodal analgesia. All patients maintained hemodynamic stability at sufficient hypnotic depth, with no observable movement during surgery or episodes of cardiac arrhythmias.

The C-MAC video stylet (Karl Storz KG, Tuttlingen, Germany) is proposed as a successor to the familiar retromolar intubation endoscope. With its flexible tip, it may be especially useful for patients with a limited mouth opening. An awake or sedated airway management technique is often preferred when a difficult airway is anticipated. Due to the challenges in preparation, sedation, topical airway anesthesia and the execution of such an airway management technique itself, these techniques are often clinically underused. The C-MAC video stylet seems to be well suited for an awake or sedated airway approach, as its handling is easier and faster than a flexible fiberscope. It does not exert pressure on the tongue as direct laryngoscopy or video laryngoscopy do. We report two cases of a difficult airway in which intubation was performed by using the C-MAC video stylet in sedated, spontaneously breathing patients. After a low dose of 3 mg midazolam IV, remimazolam was administered continuously (0.46–0.92 mg/kg/h). This was supplemented with a low dose of remifentanil (0.04–0.05 µg/kg/min). The Trachospray device (MedSpray Anesthesia BV, Enschede, The Netherlands) was used for topicalization of the upper airway by means of 4 mL of lidocaine 5%. In addition, a further 5 mL of lidocaine 5% was sprayed via an epidural catheter advanced through the oxygenation port of the C-MAC video stylet for further topicalization of the vocal cords and proximal part of the trachea. The well-coordinated steps described in these two cases may represent a blueprint and a good starting point for future studies with a larger number of patients.

Background: Variants inRYR1, the gene encoding the ryanodine receptor-1, can give rise to a wide spectrum of neuromuscular conditions. Muscle imaging abnormalities have been demonstrated in isolated cases of patients with a history of RYR1-related malignant hyperthermia (MH) susceptibility. Objective: To provide insights into the type and prevalence of muscle ultrasound abnormalities and muscle hypertrophy in patients carrying gain-of-function RYR1 variants associated with MH susceptibility and to contribute to delineating the wider phenotype, optimizing the diagnostic work-up and care for MH susceptible patients. Methods: We performed a prospective cross-sectional observational muscle ultrasound study in patients with a history of RYR1-related MH susceptibility (n = 40). Study procedures included a standardized history of neuromuscular symptoms and a muscle ultrasound assessment. Muscle ultrasound images were analyzed using a quantitative and qualitative approach and compared to reference values and subsequently subjected to a screening protocol for neuromuscular disorders. Results: A total of 15 (38%) patients had an abnormal muscle ultrasound result, 4 (10%) had a borderline muscle ultrasound screening result, and 21 (53%) had a normal muscle ultrasound screening result. The proportion of symptomatic patients with an abnormal result (11 of 24; 46%) was not significantly higher compared to the proportion of asymptomatic patients with an abnormal ultrasound result (4 of 16; 25%) (P = 0.182). The mean z-scores of the biceps brachii (z = 1.45; P < 0.001), biceps femoris (z = 0.43; P = 0.002), deltoid (z = 0.31; P = 0.009), trapezius (z = 0.38; P = 0.010) and the sum of all muscles (z = 0.40; P < 0.001) were significantly higher compared to 0, indicating hypertrophy. Conclusions: Patients with RYR1 variants resulting in MH susceptibility often have muscle ultrasound abnormalities. Frequently observed muscle ultrasound abnormalities include muscle hypertrophy and increased echogenicity.

Background: Variants in RYR1 , the gene encoding the ryanodine receptor-1, can give rise to a wide spectrum of neuromuscular conditions. Muscle imaging abnormalities have been demonstrated in isolated cases of patients with a history of RYR1 -related malignant hyperthermia (MH) susceptibility. Objective: To provide insights into the type and prevalence of muscle ultrasound abnormalities and muscle hypertrophy in patients carrying gain-of-function RYR1 variants associated with MH susceptibility and to contribute to delineating the wider phenotype, optimizing the diagnostic work-up and care for MH susceptible patients. Methods: We performed a prospective cross-sectional observational muscle ultrasound study in patients with a history of RYR1 -related MH susceptibility ( n = 40). Study procedures included a standardized history of neuromuscular symptoms and a muscle ultrasound assessment. Muscle ultrasound images were analyzed using a quantitative and qualitative approach and compared to reference values and subsequently subjected to a screening protocol for neuromuscular disorders. Results: A total of 15 (38%) patients had an abnormal muscle ultrasound result, 4 (10%) had a borderline muscle ultrasound screening result, and 21 (53%) had a normal muscle ultrasound screening result. The proportion of symptomatic patients with an abnormal result (11 of 24; 46%) was not significantly higher compared to the proportion of asymptomatic patients with an abnormal ultrasound result (4 of 16; 25%) ( P = 0.182). The mean z-scores of the biceps brachii (z = 1.45; P < 0.001), biceps femoris (z = 0.43; P = 0.002), deltoid (z = 0.31; P = 0.009), trapezius (z = 0.38; P = 0.010) and the sum of all muscles (z = 0.40; P < 0.001) were significantly higher compared to 0, indicating hypertrophy. Conclusions: Patients with RYR1 variants resulting in MH susceptibility often have muscle ultrasound abnormalities. Frequently observed muscle ultrasound abnormalities include muscle hypertrophy and increased echogenicity. Keywords Anesthesia , exertional rhabdomyolysis , malignant hyperthermia , muscle ultrasound , myopathy , RYR1 , ryanodine receptor-1

Objectives: The TensorTip (TM) MTX is a non-invasive device designed to determine several physiological parameters with additional analysis of haemoglobin, haematocrit and blood gas analysis by interpreting blood diffusion colour of the finger skin based on spectral analysis. The aim of our study was to investigate the accuracy and precision of the TensorTip MTX in a clinical setting in comparison with routine analysis of blood samples.Methods: Forty-six patients, scheduled for elective surgery, were enrolled in this study. Placement of an arterial catheter had to be part of the standard of care. Measurements were performed during the perioperative period. The measurements obtained with the TensorTip MTX were compared with the results of routine analysis of the blood samples as a reference using correlation, Bland-Altman analysis and mountain plots.Results: No significant correlation was present in the measurements. Measurement of haemoglobin with the TensorTip MTX had a mean bias of 0.4 mmol/L, haematocrit's bias was 3.0 %. Bias of partial pressure of carbon dioxide and oxygen was 3.6 and 66.6 mmHg, respectively. Calculated percentage errors were 48.2 , 48.9, 39.9 and 109.0 %. Proportional bias was present in all Bland-Altman analyses. Less than 95 % of the differences fell within the pre-set limits of allowable error.Conclusions: Non-invasive blood content analysis with the TensorTip MTX device is not equivalent to and did not correlate sufficiently with conventional laboratory analysis. None of the parameters measured showed results within the limits of allowable error. Therefore, the use of the TensorTip MTX is not recommended for perioperative care.

Background The noninvasive TensorTip™ MTX measures blood pressure by interpreting blood diffusion color of the finger skin. In addition to blood pressure, the device is able to measure various vital signs: heart rate, oxygen saturation, stroke volume, and cardiac output. Studies about accuracy and precision thus far available have only been conducted by the manufacturer. The aim of our study was to investigate the accuracy and precision of the TensorTip MTX in comparison to invasive radial artery blood pressure values. Methods Forty-one patients scheduled for elective surgery were enrolled in this study. Placement of the arterial catheter had to be part of the standard of care. Once hemodynamic stable conditions were achieved, blood pressure was measured. Three measurements with the TensorTip MTX were averaged and compared with one invasive blood pressure measurement using Bland-Altman plot and error grid analysis. Results Systolic, diastolic, and mean blood pressure had a bias of respectively 6.2, -6.9 and 4.4 mm Hg. Corresponding standard deviation were respectively 30.1, 17.0 and 22.2. Calculated percentage errors were 47.6%, 52.9% and 52.3%. Proportional bias was present in all Bland-Altman analyses. Error grid analysis showed 61.0% of systolic blood pressure measurements, and 46.3% of mean blood pressure measurements were in the clinical acceptable zone. Conclusions The TensorTip MTX was not able to reliably measure blood pressure compared to blood pressure obtained with an arterial catheter and therefore, the measurement performance is not clinically acceptable. Moreover, a high malfunction rate makes the device unsuitable for use in perioperative period.

Abstract Malignant hyperthermia and exertional rhabdomyolysis have conventionally been considered episodic phenotypes that occur in otherwise healthy individuals in response to an external trigger. However, recent studies have demonstrated a clinical and histopathological continuum between patients with a history of malignant hyperthermia susceptibility and/or exertional rhabdomyolysis and RYR1-related congenital myopathies. We hypothesize that patients with a history of RYR1-related exertional rhabdomyolysis or malignant hyperthermia susceptibility do have permanent neuromuscular symptoms between malignant hyperthermia or exertional rhabdomyolysis episodes. We performed a prospective cross-sectional observational clinical study of neuromuscular features in patients with a history of RYR1-related exertional rhabdomyolysis and/or malignant hyperthermia susceptibility (n = 40) compared with healthy controls (n = 80). Patients with an RYR1-related congenital myopathy, manifesting as muscle weakness preceding other symptoms as well as other (neuromuscular) diseases resulting in muscle weakness were excluded. Study procedures included a standardized history of neuromuscular symptoms, a review of all relevant ancillary diagnostic tests performed up to the point of inclusion and a comprehensive, standardized neuromuscular assessment. Results of the standardized neuromuscular history were compared with healthy controls. Results of the neuromuscular assessment were compared with validated reference values. The proportion of patients suffering from cramps (P < 0.001), myalgia (P < 0.001) and exertional myalgia (P < 0.001) was higher compared with healthy controls. Healthcare professionals were consulted because of apparent neuromuscular symptoms by 17/40 (42.5%) patients and 7/80 (8.8%) healthy controls (P < 0.001). Apart from elevated creatine kinase levels in 19/40 (47.5%) patients and mild abnormalities on muscle biopsies identified in 13/16 (81.3%), ancillary investigations were normal in most patients. The Medical Research Council sum score, spirometry and results of functional measurements were also mostly normal. Three of 40 patients (7.5%) suffered from late-onset muscle weakness, most prominent in the proximal lower extremity muscles. Patients with RYR1 variants resulting in malignant hyperthermia susceptibility and/or exertional rhabdomyolysis frequently report additional neuromuscular symptoms such as myalgia and muscle cramps compared with healthy controls. These symptoms result in frequent consultation of healthcare professionals and sometimes in unnecessary invasive diagnostic procedures. Most patients do have normal strength at a younger age but may develop muscle weakness later in life.

Background: During the COVID-19 pandemic in The Netherlands, critically ill ventilated COVID-19 patients were transferred not only between hospitals by ambulance but also by the Helicopter Emergency Medical Service (HEMS). To date, little is known about the impact of helicopter transport on critically ill patients and COVID-19 patients in particular. This study was conducted to explore the impact of inter-hospital helicopter transfer on vital signs of mechanically ventilated severe COVID-19 intensive care patients, with special focus on take-off, midflight, and landing.Methods: All ventilated critically ill COVID-19 patients who were transported between April 2020 and June 2021 by the Dutch ‘Lifeliner 5’ HEMS team and who were fully monitored, including noninvasive cardiac output, were included in this study. Three 10-minute timeframes (take-off, midflight and landing) were defined for analysis. Continuous data on the vital parameters heart rate, peripheral oxygen saturation, arterial blood pressure, end-tidal CO2 and noninvasive cardiac output using electrical cardiometry were collected and stored at 1-minute intervals. Data were analydzed for differences over time within the timeframes using 1-way analysis of variance. Significant differences were checked for clinical relevance.Results: Ninety-eight patients were included in the analysis. During take-off, an increase was noticed in cardiac output (from 6.7 to 8.1 Lmin-1; P<0.0001), which was determined by a decrease in systemic vascular resistance (from 1068 to 750 dyne·s·cm−5, P<0.0001) accompanied by an increase in stroke volume (from 92.0 to 110.2 ml, P<0.0001). Other parameters were unchanged during take-off and mid-flight. During landing, cardiac output and stroke volume slightly decreased (from 7.9 to 7.1 Lmin-1, P<0.0001 and from 108.3 to 100.6 ml, P<0.0001, respectively), and total systemic vascular resistance increased (P<0.0001). Though statistically significant, the found changes were small and not clinically relevant to the medical status of the patients as judged by the attending physicians.Conclusions: Interhospital helicopter transfer of ventilated intensive care patients with COVID-19 can be performed safely and does not result in clinically relevant changes in vital signs. This study was assessed by the medical ethical committee Arnhem-Nijmegen, the Netherlands (identifier 2021-7313). The committee waived the need for informed consent. The study was registered at www.trialregister.nl (identifier NL9307).