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Febrile seizures are the most common seizure disorders in children. Fever-induced hyperventilation and subsequent hypocapnia may precipitate febrile seizures. In preclinical studies and in individual children, increasing CO 2 partial pressure has shown potential to terminate febrile seizures. We hypothesized that the use of carbogen (5% CO 2 plus 95% O 2 ) in the home environment would be an effective and safe treatment for recurrent febrile seizures. The CARDIF (CARbon DIoxide against Febrile seizures) trial is a randomized, monocentric, prospective, double-blind, placebo-controlled, crossover study to determine whether short-term inhalation of carbogen in the home environment can stop febrile seizures. 100% oxygen was used as a placebo control. We included children aged 0.5 to 5.0 years who presented after a first febrile seizure in the absence of severe organ or neurological disease, pathological EEG changes, or a history afebrile seizures. We noted parent-reported seizure duration, benzodiazepine use, and any serious adverse events. We enrolled n = 92 patients. In n = 20 children, at least one recurrent febrile seizure was treated with either carbogen or oxygen . Six of these children received both carbogen and oxygen in a planned crossover design. The febrile seizure was terminated in 5/15 episodes on carbogen and in 8/11 episodes on oxygen (Fischer’s exact test; p = 0.11). Children with ≥2 recurrent febrile seizures completed the crossover arm. In these children, febrile seizures stopped during carbogen administration in 3/6 cases and during oxygen administration in 5/6 cases. In conclusion, carbogen did not interrupt acute febrile seizures more often than placebo . Home caregivers had difficulty determining when a seizure had stopped. Trial registration ClinicalTrials.gov NCT01370044

Background Current continuous kidney replacement therapy (CKRT) protocols ignore physiological renal compensation for hypercapnia. This study aimed to explore feasibility, safety, and clinical benefits of pCO2-adapted CKRT for hypercapnic acute respiratory distress syndrome (ARDS) patients with indication for CKRT. Methods We enrolled mechanically ventilated hypercapnic ARDS patients (pCO2 > 7.33 kPa) receiving regional citrate anticoagulation (RCA) based CKRT in a prospective, randomized-controlled pilot-study across five intensive care units at the Charité—Universitätsmedizin Berlin, Germany. Patients were randomly assigned 1:1 to the control group with bicarbonate targeted to 24 mmol/l or pCO 2 -adapted-CKRT with target bicarbonate corresponding to physiological renal compensation. Study duration was six days. Primary outcome was bicarbonate after 72 h. Secondary endpoints included safety and clinical endpoints. Endpoints were assessed in all patients receiving treatment. Results From September 2021 to May 2023 40 patients (80% male) were enrolled. 19 patients were randomized to the control group, 21 patients were randomized to pCO 2 -adapted-CKRT. Five patients were excluded before receiving treatment: three in the control group (consent withdrawal, lack of inclusion criteria fulfillment (n = 2)) and two in the intervention group (lack of inclusion criteria fulfillment, sudden unexpected death) and were therefore not included in the analysis. Median plasma bicarbonate 72 h after randomization was significantly higher in the intervention group (30.70 mmol/l (IQR 29.48; 31.93)) than in the control group (26.40 mmol/l (IQR 25.63; 26.88); p  < 0.0001). More patients in the intervention group received lung protective ventilation defined as tidal volume < 8 ml/kg predicted body weight. Thirty-day mortality was 10/16 (63%) in the control group vs. 8/19 (42%) in the intervention group ( p  = 0.26). Conclusion Tailoring CKRT to physiological renal compensation of respiratory acidosis appears feasible and safe with the potential to improve patient care in hypercapnic ARDS. Trial registration The trial was registered in the German Clinical Trials Register (DRKS00026177) on September 9, 2021 and is now closed.

IntroductionPeripheral arterial disease (PAD) commonly coexists with chronic kidney disease (CKD). Patients with symptomatic PAD often require endovascular revascularisation to relieve pain or salvage limbs. However, the iodinated intra-arterial contrast routinely used in these procedures is nephrotoxic, placing patients with CKD at increased risk of acute kidney injury (AKI) and long-term renal decline. Carbon dioxide (CO₂) delivered via automated injection is a potential alternative imaging contrast medium. This trial will evaluate whether using CO₂ instead of iodinated contrast reduces the risk of AKI and short-term renal function decline in this high-risk group.Methods and analysisThis is a multicentre, open-label, prospective randomised controlled trial across six secondary-care National Health Service (NHS) vascular surgery centres. A total of 174 patients with PAD and CKD undergoing endovascular intervention will be randomised 1:1 to receive iodinated contrast (standard of care) or CO₂ via automated injector (Angiodroid). All perioperative care will follow local NHS protocols.The primary outcome is log serum creatinine at 2, 30 and 90 days postprocedure. Key secondary outcomes include: incidence and severity of AKI within 48 hours postprocedure, major adverse kidney events (death, dialysis or >25% estimated glomerular filtration rate decline) by 90 days, inpatient length of stay, procedural pain, quality of life, procedural success, reinterventions, acceptability and feasibility (patient/practitioner questionnaires) of using CO2, and cost-effectiveness (healthcare resource use analysis). A mixed-methods process evaluation will be undertaken with patients and clinicians.Ethics and disseminationThe trial has been approved by an NHS ethical review committee (24/WA/0332) and patients have been involved in trial design. Findings will be disseminated to participants, clinicians and the wider public through patient groups, lay summaries, social media, conferences, peer-reviewed journals and NHS policy channels.Trial registration numberISRCTN23564393.

Objective Acne vulgaris is caused by dyslipidemia, dyskeratosis and/or abnormal bacterial growth. The obstruction of skin pores due to hyperkeratosis of the infundibulum contributes to the formation of comedones. Thus, normalizing keratinization of epidermal cells in skin pores might be useful to improve acne. Recently, it has been found that the transcutaneous application of carbon dioxide (CO2) regulates imbalances of the desquamatory process. In this study, we evaluated the efficacy of a skin lotion containing CO2 on mild acne. Methods Twenty‐four healthy Japanese males (20–29 years old) with mild acne attended this evaluation. The subjects were divided into 2 groups, one group used a skin lotion containing CO2 and the other group used a skin lotion without CO2. Following facial washing, each subject topically applied the skin lotion with or without CO2 twice a day for 4 weeks. Prior to the start of the evaluation (week 0) and following 2 and 4 weeks of treatment, acne symptoms were assessed by a dermatologist and by instrumental measurements. Results Topical application of the skin lotion with CO2 for 4 weeks significantly improved acne symptoms, which was recognized by the subjects. However, treatment with the skin lotion without CO2 did not improve acne symptoms. This improvement of acne symptoms by CO2 was not accompanied by changes in sebum levels, skin surface pH, skin capacitance, or porphyrin levels. Conclusion The transcutaneous application of a lotion with CO2 improves acne symptoms by normalizing keratinization without affecting skin surface conditions.

This study investigates the effects of radon (plus CO2) baths on RA in contrast to artificial CO2 baths in RA rehabilitation using a double-blinded trial enrolling 134 randomised patients of an in-patient rehabilitative programme (further 73 consecutive non-randomised patients are not reported here). The outcomes were limitations in occupational context/daily living (main outcome), pain, medication and further quantities. These were measured before the start, after the end of treatment and quarterly in the year thereafter. Repeated-measures analysis of covariance (RM-ANCOVA) of the intent-to-treat population was performed with group main effects (GME) and group x course interactions (G x C) reported. Hierarchically ordered hypotheses ensured the adherence of the nominal significance level. The superiority of the radon treatment was found regarding the main outcome (RM-ANCOVA until 12 months: p(GME) = 0.15, p(G x C) = 0.033). Consumption of steroids (p(GME) = 0.064, p(G x C) = 0.025) and NSAIDs (p(GME) = 0.035, p(G x C) = 0.008) were significantly reduced. The results suggest beneficial long-term effects of radon baths as adjunct to a multimodal rehabilitative treatment of RA.

Background A major challenge in treating acute asthma exacerbations is the need to open constricted airways rapidly enough to reestablish ventilation and allow delivery of conventional medication to diseased airways. The solution requires a new approach that considers both biophysical and pharmacological aspects of treatments used in acute asthma. The result of testing several formulations was S-1226: carbon dioxide-enriched air delivered in nebulized perflubron, a synthetic surfactant. These agents act synergistically to rapidly reopen closed airways within seconds. The bronchodilator effect is independent of β-adrenergic and cholinergic mediated-signaling pathways, offering a unique mechanism of action. S-1226 has a low toxicity profile and was effective in treating bronchoconstriction in animal models of asthma. The goal of the present study was to evaluate the safety and tolerability of S-1226 in healthy human subjects. Methods The phase I study was a single-center, randomized, double-blind, placebo-controlled, sequential, single-ascending-dose study conducted in Canada. Thirty-six subjects were distributed into three cohorts. Within each cohort, subjects were randomized to receive a single dose of S-1226 or a matching placebo administered over a 2-minute nebulization period. S-1226 was formulated with perflubron and 4 %, 8 %, or 12 % CO 2 . The dose of CO 2 was sequentially escalated by cohort. The safety and tolerability of S-1226 were evaluated through assessment of adverse events, vital signs, 12-lead electrocardiograms, clinical laboratory parameters, and physical examinations. Results S-1226 was safe and well tolerated at all three CO 2 levels (4 %, 8 %, and 12 %). A total of 28 adverse events were reported, and all were judged mild in severity. Twenty-four adverse events occurred in the S-1226 cohort, of which five were considered remotely related and six possibly related to S-1226. Conclusions S-1226 is a novel drug being developed for the treatment of acute asthma exacerbations. It consists of CO 2 -enriched air and perflubron and has potential to offer rapid and potent bronchodilation. The results of the study indicate that S-1226 is safe and well tolerated. All adverse events were mild, reversible, and likely due to known side effects of CO 2 inhalation. Trial registration ClinicalTrials.gov NCT02616770 . Registered on 25 November 2015.

Background Endoscopic retrograde cholangiopancreatography (ERCP) and related procedures can cause abdominal pain and discomfort. Two clinical trials have indicated, using the visual analogue scale (VAS) score, that CO 2 insufflation during ERCP ameliorates the suffering of patients without complications, compared with air insufflation. However, differences in patient suffering between CO 2 and air insufflation after ERCP under deep conscious sedation have not been reported. We focused on the gas volume score (GVS) as an objective indicator of gas volume, and designed a multicenter, prospective, double-blind, randomized, controlled study with CO 2 and air insufflation during ERCP. Methods Between March 2010 and August 2010, 80 patients who required ERCP were enrolled and evenly randomized to receive CO 2 insufflation (CO 2 group) or air insufflation (air group). ERCP and related procedures were performed under deep conscious sedation with fentanyl citrate or pethidine and midazolam or diazepam. The GVS was evaluated as the primary endpoint in addition to the VAS score as the secondary endpoint. Results The GVS after ERCP and related procedures in the CO 2 group was significantly lower than that in the air group (0.14 ± 0.06 vs. 0.31 ± 0.11, P  < 0.01), as well as the rate of increase in GVS ([GVS after − GVS before]/[GVS before ERCP and related procedures] × 100) (3.8 ± 5.9 vs. 21 ± 11.1%, P  < 0.01). VAS scores 3 and 24 h after ERCP and related procedures were comparable between the CO 2 and air groups for abdominal pain, abdominal distension, and nausea. Additionally, VAS scores were not correlated with the GVS. Conclusions CO 2 insufflation during ERCP reduces GVS (bowel gas volume) but not the VAS score of suffering compared with air insufflation. Deep and sufficient sedation during ERCP and related procedures is important for the palliation of patients’ pain and discomfort.

Background 2-8% of all children aged between 6 months and 5 years have febrile seizures. Often these seizures cease spontaneously, however depending on different national guidelines, 20-40% of the patients would need therapeutic intervention. For seizures longer than 3-5 minutes application of rectal diazepam, buccal midazolam or sublingual lorazepam is recommended. Benzodiazepines may be ineffective in some patients or cause prolonged sedation and fatigue. Preclinical investigations in a rat model provided evidence that febrile seizures may be triggered by respiratory alkalosis, which was subsequently confirmed by a retrospective clinical observation. Further, individual therapeutic interventions demonstrated that a pCO 2 -elevation via re-breathing or inhalation of 5% CO 2 instantly stopped the febrile seizures. Here, we present the protocol for an interventional clinical trial to test the hypothesis that the application of 5% CO 2 is effective and safe to suppress febrile seizures in children. Methods The CARDIF ( CAR bon DI oxide against F ebrile seizures) trial is a monocentric, prospective, double-blind, placebo-controlled, randomized study. A total of 288 patients with a life history of at least one febrile seizure will be randomized to receive either carbogen (5% CO 2 plus 95% O 2 ) or placebo (100% O 2 ). As recurrences of febrile seizures mainly occur at home, the study medication will be administered by the parents through a low-pressure can fitted with a respiratory mask. The primary outcome measure is the efficacy of carbogen to interrupt febrile seizures. As secondary outcome parameters we assess safety, practicability to use the can, quality of life, contentedness, anxiousness and mobility of the parents. Prospect The CARDIF trial has the potential to develop a new therapy for the suppression of febrile seizures by redressing the normal physiological state. This would offer an alternative to the currently suggested treatment with benzodiazepines. This study is an example of academic translational research from the study of animal physiology to a new therapy. Trial registration ClinicalTrials.gov identifier: NCT01370044

There is no consensus regarding treatment modalities for idiopathic sudden sensorineural hearing loss (SNHL). In order to evaluate the effectiveness of steroid or carbogen inhalation therapies, a prospective double-blind placebo controlled study was designed. All 41 patients enrolled in the study had unilateral SNHL with no prior history of SNHL, otological pathological history or otoscopic findings. Patients were assigned to four treatment groups: prednisone tablets, placebo tablets, carbogen inhalation or room air inhalation. All were treated for 5 days. The audiometric data at admission was compared to that at day 6 and to data collected at follow-up (average 33 days). Results revealed no significant difference between the groups for early or late audiometric outcome. Age, time from onset of symptoms to initiation of treatment, tinnitus, audiogram configuration, and the presence of vertigo at onset did not significantly affect the outcome. The discrimination scores that were poor in all patient groups on admission improved within days in all groups. These findings suggest that steroids or carbogen inhalation have no therapeutic advantage over placebo. Also, regardless of treatment modality, hearing continued to improve for at least a month after treatment was stopped.

To compare the therapeutic effect of fractional carbon dioxide (CO2) laser + topical triamcinolone (TA) with intralesional TA on keloids. Twenty‐two participants were randomised into two groups: group A, treated with fractional CO2 laser + topical TA, and group B, treated with intralesional TA. The interventions were performed at every 4‐week interval until the keloids were resolved or at the completion of 1 year. At each session, the scar volume, Vancouver Scar Scale (VSS) were assessed. Recurrence was observed for 1 year. The mean scar volumes and VSS scores were not significantly different between the two groups. After 1 year, the scar volume change in group B was greater than group A (86.5% vs 59.1%, P‐value = .016). The mean VSS scores were significantly decreased in group A (8.0 ± 1.5 to 4.8 ± 1.6, P‐value <.001) and group B (8.4 ± 0.8 to 4.8 ± 1.6, P‐value <.001). The keloids were completely resolved in 63.6% and 72.7% of the patients, and recurrence was observed in 9.1% and 18.2% of the patients in groups A and B, respectively. The combination of fractional CO2 laser with topical TA was an alternative option for the treatment of keloids.