Impact of drug and equipment preparation on pre-hospital emergency Anaesthesia (PHEA) procedural time, error rate and cognitive load

Background We examined the effect of advanced preparation and organisation of equipment and drugs for Pre-hospital Emergency Anaesthesia (PHEA) and tracheal intubation on procedural time, error rates, and cognitive load. Methods This study was a randomised, controlled experiment with a crossover design. Clinical teams (physician and paramedic) from the Emergency Medical Retrieval Service and the Scottish Air Ambulance Division were randomised to perform a standardised pre-hospital clinical simulation using either unprepared (standard practice) or pre-prepared (experimental method) PHEA equipment and drugs. Following a two-week washout period, each team performed the corresponding simulation. The primary outcome was intervention time. Secondary outcomes were safety-related incidents and errors, and degree of cognitive load. Results In total 23 experiments were completed, 12 using experimental method and 11 using standard practice. Time required to perform PHEA using the experimental method was significantly shorter than with standard practice (11,45 versus 20:59) minutes: seconds; p = < 0.001). The experimental method also significantly reduced procedural errors (0 versus 9, p = 0.007) and the cognitive load experienced by the intubator assistant (41.9 versus 68.7 mm, p = 0.006). Conclusions Pre-preparation of PHEA equipment and drugs resulted in safer performance of PHEA and has the potential to reduce on-scene time by up to a third. Electronic supplementary material The online version of this article (10.1186/s13049-018-0549-3) contains supplementary material, which is available to authorized users.


SIGNATURE PAGE Chief Investigator Agreement
The clinical study as detailed within this research protocol (Version 1, 08 Nov 16), or any subsequent amendments will be conducted in accordance with the Research Governance

Methodology
Type of study: Randomised control experiment with a cross-over design

Research Sites
Scottish Ambulance Service, ScotSTAR

Objectives / Aims
Compare the effect on time and safety to set up equipment (kit dump), and place an endotracheal tube during a simulated prehospital scenario. Using different equipment configurations for pre-hospital Rapid Sequence Induction of anaesthesia (RSI). The primary outcome on total intervention time (seconds) and secondary outcomes on safety-related incidents and errors, along with degree of cognitive load, satisfaction, and difficulty scores.

Number of Participants/Pa tients
24 participants forming 12 two person teams (a physician and a paramedic).

Main Inclusion Criteria
Retrieval Physicians: • Currently working with the adult retrieval service of ScotSTAR -Emergency Medical Retrieval Service (EMRS).
• Greater than 6 months' experience as a consultant physician with EMRS.
• Assessed by EMRS to be competent and current at preparing a kit dump for pre-hospital RSI.

Helicopter emergency services (HEMS) Paramedics:
• Currently working for the Scottish Ambulance Service air ambulance division alongside EMRS.
• Greater than 6 months' experience as a HEMS paramedic.
• Minimum of 8 years' frontline ambulance experience.

Methodology and Analysis (if applicable)
Distribution of data will be assessed using normal quartile plots (or an appropriate test).
However, we are aware that each of these statistical tests have their own limitations.

If data is parametric then:
Catagorical data compared using Chi 2 , continuous data compared with Student T.

If non-parametric then:
Catagorical data compared with Fischer Exact, continuous data compared with Wilcoxon matched-pair signed-rank test.
Primary outcome will compare the mean total intervention time to completion of the process by standard practice vs experimental method. p-value will be set at <0.05 for statistical significance.

INTRODUCTION
Rapid Sequence Induction of anaesthesia (RSI) in any environment is associated with significant risks including hypoxia, hypotension, or failure to secure an airway. Most of these complications are predictable, and the risk can be greatly reduced with appropriate preparation. In controlled environments, for example the induction of anaesthesia for elective surgery, these risks are extremely low. However, in uncontrolled environments these risks are more likely to increase.
A potential source of error in pre-hospital RSI is the preparation of the required equipment and drugs. Pre-hospital time is an essential factor in the initial care of critically injured/ill patients, and is directly related to mortality. Time saving interventions are therefore beneficial.
One of the principal aims of pre-hospital care is to balance the need for appropriate intervention with the need to transport patients to definitive care.
This study will evaluate the effectiveness of a new method of working, having all necessary equipment and drugs prepared and organised prior to the procedure being required, to investigate whether the improved pre-preparation will make this process faster, while still resulting in the safe placement of endotracheal tubes.

TRIAL OBJECTIVES
Research Questions: • Does pre-preparing drugs and equipment for pre-hospital rapid sequence induction of anaesthesia and tracheal intubation (PRSI) impact the time it takes to safely place an endotracheal tube?
• Does pre-preparing drugs and equipment for pre-hospital RSI impact the error rate (safety)? Objective: Compare the effect on time and safety to set up equipment (kit dump) and place an endotracheal tube during a simulated prehospital scenario. Using different equipment configurations for pre-hospital Rapid Sequence Induction of anaesthesia (RSI). The primary outcome on total intervention time (seconds) and secondary outcomes on safety related incidents and errors, along with degree of cognitive load, satisfaction, and difficulty scores.

Definitions / Endpoints
-Primary • Total intervention time (seconds) -defined in this study, from the decision to preform RSI to confirming placement of endotracheal tube (breathing tube) with the measure of end-tidal capnography (concentration of carbon dioxide at the end of an exhaled breath). -Secondary • Component times (seconds) -being the time taken for each component of the process (table 1) to include preparation of airway equipment and drug preparation, checklist, drug administration, onset time, tracheal intubation.

• Safety related incidents
• Procedural errors, defined as error in the preparation or use of medications or equipment with the potential to result in harm an unintended/unexpected incident, which led, or could have led to harm.
Errors will be counted and classified according to table 2.
• Procedural lapse, defined as a failure to execute an action due to lapse in memory and a routine behaviour being omitted. Lapse will be counted and classified according to table 2 • Degree of cognitive load -Subjective estimate, using a visual analogue scale, of the amount of cognitive work the procedure entailed. Cognitive load will be defined for the participant as the amount of cognitive work/energy required to complete the procedure, including the level of judgements/decisions needing to be made.

Inclusion Criteria
Eligible participants are experts in prehospital care, and perform RSI as part of their normal working practice. They will be retrieval consultant physicians recruited from Scotland's National Retrieval Service (ScotSTAR) and Helicopter Emergency Services (HEMS) Paramedics employed by the Scottish Ambulance Service.
Each participant will be emailed an invitation that includes an information sheet about the nature of the study; consenting participants are then enrolled.
Participants will be randomly assigned into 12 teams of two (a physician and a paramedic) using computer randomisation. Each team will be asked to perform an RSI on a mannequin in a simulated pre-hospital setting.
The trial will comprise of a traditional set-up of a drug bag containing all the required drug vials, syringes and labels to prepare for a pre-hospital RSI, and a conventional airway bag holding all the required airway equipment, versus the new experimental set-up using a new method of working, having all necessary equipment and drugs prepared and organised prior to the procedure being required.
Each team will use both set-ups sequentially during the two scenarios, their starting process (standard practice or experimental method) being decided randomly using computer batch randomisation. To reduce exposure bias and training artefact there will be a minimum period of two weeks between the first and the second scenario. The allocation will be conveyed to the participant in sequential-numbered opaque envelopes, and undertaken independently for each participant group to ensure an adequate number of participants in each arm.
Before commencing their assigned arm of the study each team will be briefed on what is needed and provided as much time as required to prepare, and ask questions. A picture of a kit dump will be used to indicate what is required and standardize the briefing.
The time taken to complete the process will be measured and the difference between the two set-ups compared, along with safety, errors, and degree of cognitive load, satisfaction, and difficulty scores received from the participants. It is anticipated that this process will take approximately 1 hour of each participants' time. To accurately measure the outcomes, filming will be used, solely for review by the investigators, and then destroyed.
The investigator will record: • Total intervention time (seconds) -defined in this study, from the decision to preform RSI to confirming placement of endotracheal tube (breathing tube) with the measure of end-tidal capnography (concentration of carbon dioxide at the end of an exhaled breath).
• Component times (seconds) -being the time taken for each component of the process (table 1) to include preparation of airway equipment and drug preparation, checklist, drug administration, onset time, tracheal intubation.
• Procedural errors, defined as error in the preparation or use of medications or equipment with the potential to result in harm an unintended/unexpected incident, which led, or could have led to harm. Errors will be counted and classified according to • Procedural lapse, defined as a failure to execute an action due to lapse in memory and a routine behaviour being omitted. Lapse will be counted and classified according to • The degree of individual cognitive load (ICL), defined as the amount of cognitive work/energy required by the participant to complete the procedure, including the level of judgements/decisions needing to be made will be measured.

Component times Equipment Preparation
Total time taken to setup the airway equipment, from touching the airway bag to completing the equipment setup.

Drug Preparation
Total time to prepare the drugs, from touching the drug bag to completing the preparation of the drugs.
Checklist Total time to complete the checklist, from the point of starting the checklist to completing the last sentence of the checklist.

Drug Administration
Total time taken to administer the drugs, from picking up the syringe to complete administration of Alfentanil, Ketamine and Rocuronium.

Drug Onset Time
The time it takes for drugs to reach maximal effect, for optimal intubation conditions (60sec), from the administration of Rocuronium to the decision to attempt intubation.

Tracheal Intubation
Placement of an endotracheal tube into the trachea, under direct laryngoscopy, confirmed by visualising it pass through the vocal cords, by auscultation and by the measure of quantitative EtCO 2

Exclusion Criteria
Clinicians who have less than 6 months experience working with or alongside the adult retrieval service (EMRS).
Clinicians who have not been assessed by EMRS to be competent and current at preparing a kit dump for pre-hospital Rapid Sequence Induction of anesthesia (PRSI).

Study Design / Plan -Study Visits
Eligible participants are experts in prehospital care, and perform RSI as part of their normal working practice. They will be retrieval physicians recruited from Scotland's National Retrieval Service (ScotSTAR) and Helicopter Emergency Services (HEMS) Paramedics employed by the Scottish Ambulance Service.
Each participant will be emailed an invitation that includes an information sheet about the nature of the study; consenting participants are then enrolled.
Participants will be randomly assigned into 12 teams of two (a physician, and a paramedic) using computer randomisation.

Informed Consent Procedures and Enrollment
All the voluntary participants are consenting adults, each of whom will firstly have received an information sheet pertaining to this study. In accordance with the Data Protection Act 1998. We will follow ethical and legal practice, all information which is collected about the participant during the research will be kept strictly confidential.
Participants will be allocated a unique study reference number and all data collected will be stored under this number, including questionnaire responses. Participants will also be informed, that filming will be used to accurately measure the outcomes which will only be reviewed by the investigators, after which it will be destroyed. Identifiable electronic data will be stored on an NHS computer in a password protected domain. This information will only be accessible to the researcher.
Each of the participants will be briefed on what they will be expected to do during the study, and advised how their anonymised data will be used. The participant is free to withdraw at any stage, and should they decide to withdraw all their data will be destroyed and will not be included in any subsequent publication.
They will be provided time to ask any questions and once they are happy to proceed the participant will sign a consent form prior to starting.

Randomization Procedures
Each participant (physician and paramedic) will be randomly appointed using computer randomisation into a two-person (physician, paramedic) team.
In addition, computer batch randomisation will be undertaken to establish the first process which would be undertaken by the team (standard practice or experimental arm). The allocation will then be conveyed to the participants by means of sequential numbered opaque envelopes. To ensure adequate inclusion of each team to both arms of the study, this process will be undertaken independently for each participant team.

End of Study Definition
Once all the teams have completed both arms of the study.

STATISTICAL CONSIDERATIONS
Sample Size for the study. 24 participants forming 12 two person teams.
Statistical explanation for sample size for the study.
-Sample size was calculated using data from observation of prior EMRS practice: in ten consecutive standard PRSI's, measuring 16:03 to 24:28 minutes: seconds, the mean procedural time was 20:03 minutes: seconds and standard deviation of 3:26 minutes: seconds.
-A 20% reduction in procedural time would be considered clinically significant.
-From this information, the sample size needed for the paired t-test to have a 90% chance of detecting a difference in means of four minutes at a level of significance of 5% (twosided), is 11 samples. To allow for any exclusions the sample size is adjusted to twelve simulations in each arm.
- Distribution of data will be assessed using normal quartile plots (or an appropriate test).

Method of Analysis
However, we are aware that each of these statistical tests have their own limitations.

If data is parametric then:
Categorical data compared using Chi 2 , continuous data compared with Student-T.

If non-parametric then:
Categorical data compared with Fischer Exact, continuous data compared with Wilcoxon matched-pair signed-rank test.
-Primary Outcome • will compare the mean total intervention time to completion of the process by standard practice vs experimental method. p-value will be set at <0.05 for statistical significance.
-Secondary outcomes • Component times (seconds) -being the time taken for each component of the process (table 1) by standard practice vs experimental method.
• Safety related incidents • Procedural errors, will be counted and classified according to table 2 by standard practice vs experimental method.
• Procedural lapse, will be counted and classified according to table 2 by standard practice vs experimental method.
• Degree of cognitive load -will be measured using 100mm visual analog score, comparing the mean satisfaction, degree of cognitive load by standard practice vs experimental method.

-Primary Endpoint
• Total intervention time (minutes: seconds) -defined in this study as starting at the decision to perform PRSI and ending when correct ETT position, confirmed with the facilitator turning on the EtCO 2 simulation software, in response to visualising chest inflation.

-Secondary Endpoint
• Component times (seconds) -Time taken to complete each of the components of the procedure are presented in table 1.
• Procedural errors, defined as an unintended/unexpected incident, which led, or could have led to harm. Errors were counted and classified according to table 2.
• Individual cognitive load (ICL), defined as the amount of cognitive work/energy required by the participant to complete the procedure, including the level of judgements/decisions needing to be made will be measured. ICL will be measured using visual analogue score (VAS). At the end of each simulation, participants will be asked to record their perceived degree of cognitive load during PRSI on a standard 100-mm line (0-mm representing no cognitive load and 100-mm representing maximal cognitive load) comparing the means with the process by standard practice vs experimental method.

ETHICS
The Principal Investigator will ensure that the study will be carried out in accordance with All the voluntary participants are consenting adults, each of whom will firstly have received an information sheet pertaining to this study. In accordance with the Data Protection Act 1998. We will follow ethical and legal practice, all information which is collected about the participant during the research will be kept strictly confidential.
Participants will be allocated a unique study reference number and all data collected will be stored under this number, including questionnaire responses. Participants will also be informed, that filming will be used to accurately measure the outcomes which will only be reviewed by the investigators, after which it will be destroyed. Identifiable electronic data will be stored on an NHS computer in a password protected domain. This information will only be accessible to the researcher.
Each participant will be briefed on what they will be expected to do during the study, and advised how their anonymised data will be used. They will be provided time to ask any questions, once satisfied to proceed they will sign a consent form prior to starting. The participant is free to withdraw at any stage, and should they decide to withdraw all their data will be destroyed and will not be included in any subsequent publication.

Include details of any conflicts of interest.
The airway bag (SCRAM ® bag) which is used in the experimental group of this study was technologies that aim to improve patient care and generate income for NHS Scotland.
• SHIL have helped us develop an idea into a product, that is now commercially available.
Where 1/3 of the proceeds go to the employer (SAS), 1/3 is equally divided between the inventors and the remaining goes to the manufacturer.
• SHIL have also funded the cost (£872) of the consumables for this study.

SAFETY CONSIDERATIONS:
During the simulated preparation of the kit dump for emergency prehospital anaesthesia, the participants will be expected to draw up drugs, which is part of their everyday practice and these experienced clinicians are aware of safe sharps management. Nevertheless, all participants will be reminded to adhere to the safe practice and working with sharps.
However, in the event a sharps injury is sustained a first aid kit will be available.

DATA HANDLING AND RECORD KEEPING:
-Confidentiality In accordance with the Data Protection Act 1998. We will follow ethical and legal practice, all information which is collected about the participant during the course of the research will be kept strictly confidential and managed in accordance with the Data Protection Act, NHS Caldecott Principles, The Research Governance Framework for Health and Social Care, and the conditions of Research Ethics Committee Approval. Participants will be allocated a unique study reference number and all data collected will be stored under this number, including questionnaire responses. Identifiable electronic data will be stored on an NHS computer in a password protected domain. This information will only be accessible to the researcher.
The lever arch file containing the enrolment forms and raw data will be secured in a locked filing cabinet at the ScotSTAR base (address below) where only the principle investigator has access to.
To accurately measure the outcomes, filming will be used and will be reviewed by investigators to accurately record the timings of elements of the procedure, after which it will be destroyed. -

Record Retention and Archiving
The data generated by the study will be stored for 5 years on an NHS computer in a password protected domain.
The lever arch file containing the enrolment forms and raw data will be secured in a filing cabinet at the ScotSTAR base (address below) where only the chief investigator has access to.
No recorded film will be retained. In accordance with the data protection act 1998. At the end of the study all personal enrolment data will be securely destroyed.

Techniques and interventions
In both arms of the experiment, the clinical team will be asked to perform performed PRSI on a mannequin, presented within a realistic pre-hospital clinical simulation (Appendix 3).
This included the decision to RSI, and the performance of the procedure according to the services (SOP).

Tools
Following the simulation, participants will complete a questionnaire (100mm analogue scale) measuring cognitive load, satisfaction, and difficulty.

Adverse Events (AE)
An AE is any untoward medical occurrence in a subject to whom a medicinal product has been administered, including occurrences which are not necessarily caused by or related to that product. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporarily associated with study activities.

Notification and reporting Adverse Events or Reactions
If the AE is not defined as SERIOUS, the AE is recorded in the study file and the participant is followed up by the research team. The AE is documented in the participants' medical notes (where appropriate) and the CRF.

Serious Adverse Event (SAE)
In other research other than CTIMPs, a serious adverse event (SAE) is defined as an untoward occurrence that: (a) results in death; (b) is life-threatening; (c) requires hospitalisation or prolongation of existing hospitalisation; (d) results in persistent or significant disability or incapacity; (e) consists of a congenital anomaly or birth defect; or (f) is otherwise considered medically significant by the investigator.
An SAE occurring to a research participant should be reported to the main REC where in the opinion of the Chief Investigator the event was: • Related -that is, it resulted from administration of any of the research procedures, and • Unexpected -that is, the type of event is not listed in the protocol as an expected occurrence.

Notification and Reporting of Serious Adverse Events
Serious Adverse Event (SAEs) that are considered to be 'related' and 'unexpected' are to be reported to the sponsor within 24 hours of learning of the event and to the Main REC within 15 days in line with the required timeframe.

Urgent Safety Measures
The CI may take urgent safety measures to ensure the safety and protection of the clinical trial subjects from any immediate hazard to their health and safety. The measures should be taken immediately. In this instance, the approval of the REC prior to implementing these safety measures is not required. However, it is the responsibility of the CI to inform the sponsor and Main Research Ethics Committee (via telephone) of this event immediately.
The CI has an obligation to inform both the Main REC in writing within 3 days, in the form of a substantial amendment. The sponsor (Joint Research Management Office [JRMO]) must be sent a copy of the correspondence with regards to this matter.

Annual Safety Reporting
The CI will send the Annual Progress Report to the main REC using the NRES template (the anniversary date is the date on the MREC "favourable opinion" letter from the MREC) and to the sponsor.

Overview of the Safety Reporting responsibilities
The CI/PI has the overall pharmacovigilance oversight responsibility. The CI/PI has a duty to ensure that safety monitoring and reporting is conducted in accordance with the sponsor's requirements.
Safety will be monitored in accordance with standard NHS health and safety procedures.
Safety will be reviewed on a case by case basis to establish if any interventions are required.
In view of the small sample size and service evaluation methodology for this study, interim analysis of efficacy is not indicated.
What are the criteria for electively stopping the trial or other research prematurely?
Clear evidence of participant risk or an instance of significant injury to a participant will prompt a safety stop and review. Such a stop would be reviewed at local and QMUL level with regard to continuing the study with appropriate modifications to protect the participants with a view to achieving the primary outcome measures. Failing this the trial would be terminated by the PI at the sole site.

MONITORING & AUDITING
This is a single site study which will be overseen by the PI and team who will be responsible for conduct of the research. Overall monitoring will be undertaken by the QMUL with local oversight from the ScotSTAR R&D group. Definition: "A systematic and independent examination of trial related activities and documents to determine whether the evaluated trial related activities were conducted, and the data were recorded, analysed and accurately reported according to the protocol, sponsor's standard operating procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s)." • SHIL have helped us develop an idea into a product, that is now commercially available. Where 1/3 of the proceeds go to the employer (SAS), 1/3 is equally divided between the inventors and the remaining goes to the manufacturer.
• SHIL have also funded the cost (£872) of the consumables for this study.

INDEMNITY
Queen Mary University of London

DISSEMINATION OF RESEARCH FINDINGS:
This study would be relevant to clinicians in the following fields: • Airway management • Pre-hospital medicine • Aeromedical services • Retrieval services • Trauma services • Emergency Medicine

REFERENCES
AMA/Vancouver format using Endnote referencing management software.

APPENDICIES
Are stand-alone documents:

1) Simulation (Appendix S2)
The following journal may be considered for publication