ORAL-PROTECT I: Oral Asepsis Preventing Transmission During Intubation

Official title

ORAL-PROTECT I: Oral Asepsis for Preoperative Reduction Of Tracheal Bacterial Establishment, Colonization, and Transmission

Overview

Postoperative respiratory complications, such as bacterial pneumonia, are common and serious problems after general anesthesia. They can lead to longer hospital stays, more complications, and increased mortality. One possible cause is that bacteria from the mouth and throat enter the lower airways during tracheal intubation. The mouth and throat naturally contain many bacteria, including potentially harmful microorganisms. During general anesthesia, coughing and swallowing reflexes are reduced or absent. When a tracheal tube is inserted, secretions from the mouth and throat may be carried into the trachea. The tube may also support the movement of contaminated fluid into the lower airways. ORAL-PROTECT I is a prospective, randomized, controlled study. It investigates whether simple oral hygiene before surgery can reduce the transfer of bacteria into the trachea during airway management under general anesthesia. The study includes patients aged 60 years or older undergoing elective surgery under general anesthesia with tracheal intubation. Participants are randomly assigned to an intervention group or a control group. The intervention group performs oral hygiene immediately before anesthesia. This includes brushing the teeth and tongue for about 3 minutes, followed by rinsing and gargling for about 1 minute with a chlorhexidine antiseptic solution. The control group receives standard care without additional oral hygiene. Oral, pharyngeal, and tracheal swabs will be collected at predefined time points. The primary outcome is based on the perioperative tracheal bacterial load, sampled every 30 minutes and assessed at two hours after induction of anesthesia. The co-primary outcome is based on the oral bacterial load immediately before endotracheal intubation. Secondary outcomes include changes in oral and tracheal bacterial load over time and identification of the microorganisms detected. The study aims to clarify early bacterial transfer during airway management and to evaluate whether a simple preoperative oral hygiene measure can reduce this process.

Detailed description

ORAL-PROTECT I is a prospective, randomized, controlled, unblinded, parallel-group trial investigating whether preoperative oral hygiene can reduce early bacterial transmission from the mouth and throat into the trachea during airway management under general anesthesia.

Postoperative respiratory complications, including bacterial pneumonia, are common and clinically relevant adverse events after general anesthesia. They can contribute to increased morbidity, prolonged hospital stay, and mortality. One possible mechanism is the transmission of bacteria from the oral cavity and pharynx into the lower airways during tracheal intubation. The oral cavity and pharynx naturally contain a broad bacterial flora, including potentially pathogenic microorganisms. During general anesthesia, protective swallowing and coughing reflexes are reduced or absent. During tracheal intubation, bacteria-contaminated secretions from the mouth and throat may enter the trachea and lower airways.

The study includes patients aged 60 years or older undergoing elective surgery under general anesthesia with tracheal intubation. Potentially eligible patients are screened before surgery. Patients are screened for eligibility during pre-admission testing and are approached for study participation. On the day of surgery, patients are reassessed for eligibility before randomization to confirm that eligibility criteria are still met. Patients who performed oral hygiene less than four hours before induction are excluded before randomization.

Eligible participants are randomly assigned to either the intervention group or the control group using a REDCap-based randomization tool. Participants in the intervention group undergo supervised oral hygiene immediately before induction of anesthesia, consisting of 3 minutes of tongue and tooth brushing and 1 minute of chlorhexidine gargling. Participants in the control group receive standard clinical care without additional preoperative oral hygiene measures. All other perioperative procedures, including anesthetic management, airway management, surgical care, and postoperative treatment, are at the discretion of the treating anesthesiologist and independent of study participation.

Bacterial load is assessed using swab-based microbiological sampling at predefined time points. Samples are collected from the oral cavity, pharynx, and trachea to describe perioperative bacterial contamination and its development over time. The perioperative tracheal bacterial load is sampled at 30-minute intervals.

Sample handling and microbiological processing follow a standardized operating procedure. This includes uniform transport conditions, timely laboratory processing, neutralization of residual antiseptic activity, serial dilution, plating on appropriate culture media, aerobic incubation, and quantitative colony counting. Samples from both study groups are processed identically to minimize systematic bias and allow reliable comparison of bacterial load. Additional assessments include the intraoperative course of tracheal bacterial load, tracheal bacterial load before extubation, oral bacterial load approximately 24 hours after surgery, and qualitative microbiological characterization of detected bacteria. Adverse events are evaluated after the intervention and anesthesia.

The study aims to provide insight into early perioperative bacterial transmission during airway management and to evaluate whether a simple, low-risk preoperative oral hygiene intervention can influence bacterial contamination of the trachea under general anesthesia.

Interventions

• Procedure Preoperative oral decontamination with chlorhexidine
  The intervention consists of supervised preoperative oral decontamination performed in the operating room holding/ induction area immediately before induction of general anesthesia. Participants brush their teeth and tongue for 3 minutes, followed by a rinse with chlorhexidine oral antiseptic solution for 1 minute. The intervention is performed right before endotracheal intubation. All other perioperative procedures are at the discretion of the anesthesiologist in the room.

Primary outcome measures

• Change in tracheal bacterial load at 2 hours after anesthesia induction [Time frame: At 2 hours after induction and intubation]
• Change in oral bacterial load [Time frame: Immediately before endotracheal intubation.]

Secondary outcome measures (5)

• Intraoperative development of tracheal bacterial load [Time frame: Every 30 minutes intraoperatively from endotracheal intubation until washout of anesthesia prior to extubation.]
• Change of tracheal bacterial load immediately before extubation [Time frame: Immediately before extubation.]
• Change of oral bacterial load 24 hours postoperatively [Time frame: Approximately 24 hours postoperatively, with a tolerance of ±2 hours.]
• Qualitative microbiological characterization of bacteria detected in tracheal samples [Time frame: Tracheal swabs are obtained from right after intubation until extubation. For the primary outcome all samples are plated. If Colony Forming Units (CFU) occur on those within 48 hours, characterization will be performed.]
• Safety events related to the oral hygiene intervention [Time frame: From the start of the oral hygiene intervention until approximately 24 hours postoperatively.]

Eligibility criteria

Inclusion criteria

• Age ≥ 60 years
• Elective surgery under general anesthesia with endotracheal intubation
• Expected duration of surgery ≥ 2 hours
• Ability to provide written informed consent

Exclusion criteria

• Systemic antibiotic therapy within 7 days before surgery
• Planned postoperative systemic antibiotic therapy
• Known hypersensitivity or allergy to chlorhexidine
• Pneumonia or clinically relevant respiratory infection within 7 days before surgery
• Inability to perform the study intervention as intended
• Preoperative oral hygiene on the day of surgery, less than four hours prior to induction of the general anesthesia

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

Germany · 1 center

• Ulm University Medical Center, Department of Anesthesiology and Intensive Care Medicine — Ulm

Publications

• Naumova EA, Weber L, Pankratz V, Czenskowski V, Arnold WH. Bacterial viability in oral biofilm after tooth brushing with amine fluoride or sodium fluoride. Arch Oral Biol. 2019 Jan;97:91-96. doi: 10.1016/j.archoralbio.2018.10.013. Epub 2018 Oct 17. PMID 30368202
• Shuai Y, Wang X, Chen S, Huang T, Wang Z, Zhang Y. Preoperative oral hygiene treatment reduces bacterial transport and colonization during intubation for orthopedic surgery. J Oral Sci. 2024;66(2):134-138. doi: 10.2334/josnusd.23-0425. PMID 38631883
• Okochi M, Nomura S, Kaga C, Honda H. Peptide array-based screening of human mesenchymal stem cell-adhesive peptides derived from fibronectin type III domain. Biochem Biophys Res Commun. 2008 Jun 20;371(1):85-9. doi: 10.1016/j.bbrc.2008.04.019. Epub 2008 Apr 14. PMID 18413142
• Pneumatikos IA, Dragoumanis CK, Bouros DE. Ventilator-associated pneumonia or endotracheal tube-associated pneumonia? An approach to the pathogenesis and preventive strategies emphasizing the importance of endotracheal tube. Anesthesiology. 2009 Mar;110(3):673-80. doi: 10.1097/ALN.0b013e31819868e0. PMID 19212256
• Fourrier F, Duvivier B, Boutigny H, Roussel-Delvallez M, Chopin C. Colonization of dental plaque: a source of nosocomial infections in intensive care unit patients. Crit Care Med. 1998 Feb;26(2):301-8. doi: 10.1097/00003246-199802000-00032. PMID 9468169
• Scannapieco FA, Stewart EM, Mylotte JM. Colonization of dental plaque by respiratory pathogens in medical intensive care patients. Crit Care Med. 1992 Jun;20(6):740-5. doi: 10.1097/00003246-199206000-00007. PMID 1597025
• Cozowicz C, Zhong H, Reisinger L, Illescas A, Giannakis P, Liu J, Poeran JV, Memtsoudis SG. Inpatient Cost of Complications after Total Hip and Knee Arthroplasty. Anesthesiology. 2026 Mar 1;144(3):611-621. doi: 10.1097/ALN.0000000000005856. Epub 2025 Nov 20. PMID 41264388
• Martin CT, Gao Y, Pugely AJ. Incidence And Risk Factors For 30-Day Readmissions After Hip Fracture Surgery. Iowa Orthop J. 2016;36:155-60. PMID 27528853

Identifiers

NCT: NCT07669064 · Ethical Committee Number 23/26

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗