RELIABILITY AND SOURCE OF ERRORS IN END-TIDAL GAS CONCENTRATION EVALUATION ALGORITHMS DURING AVALANCHE SNOW AND REBREATHING EXPERIMENTS

Summary

During breathing experiments in avalanche snow, measurement of CO₂ is often conducted in order to monitor the volunteers or as an endpoint of the trial. From the measured CO₂ signal, monitors calculate end-tidal CO₂ concentrations (EtCO₂). The aim of the study was to investigate several related points: to determine if the Datex-Ohmeda S/5 anesthesia monitor evaluates EtCO₂ and other parameters of breathing gas correctly, to characterize the frequency and magnitude of error and to determine the possible cause of the error. Data from a previous experiment aimed at investigation of work of breathing into snow in the presence and absence of an artificial air pocket were used to study accuracy of the monitor. The analysis found that an error of EtCO₂ occurred in 39% and in 30% of the total experimental time of breathing, with and without the air pocket respectively (range from 13% to 93% of time). Breathing experiments with simulated snow were conducted in order to find the cause of the error. We determined the error occurs immediately after a significant increase of CO₂ in the breathing circuit as a consequence of expired gas rebreathing and is independent of other breathing parameters. The study confirmed that a newer model monitor (CARESCAPE B650) is prone to this error as well. The last experiment conducted with a standard anesthesia machine confirmed, that the error occurs even in a standard clinical setup in the presence of rebreathing. This problem might result in improper actions and could potentially result in harm to a volunteer or a patient.

Keywords:
hypercapnia, EtCO₂, avalanche, snow burial, device error, Datex S/5, CARESCAPE B650

Introduction

As avalanche burials represent one of the most dangerous risks associated with winter activities in the mountains, research of survival circumstances and possibilities how to improve the survival rate represent topical research questions. The probability of survival rapidly decreases with time [1, 2]. When a victim repetitively inspires previously expired gas, the inhaled gas gradually contains less oxygen and higher concentration of carbon dioxide. This condition leads to asphyxiation as the dominant cause of avalanche-related deaths [3–5].

Recently published experiments, trying to describe the dynamics of asphyxiation in the snow, often measure physiological parameters of the volunteers participating in the research. The concentrations of gases in the inspired and expired gas are the primary parameters determining the dynamics of asphyxiation.

Brugger et al. [6] conducted an experiment in 12 volunteers breathing into snow pockets of volume 1 L or 2 L while they measured changes in peripheral oxygen saturation (SpO₂) and end-tidal concentration of carbon dioxide (EtCO₂). SpO₂ and EtCO₂ were
also selected as primary endpoints in this study. Hypercapnia and its effects on hypothermia during snow burial were studied by Grissom et al. [7]. Hypercapnia increased a cooling rate of the body. EtCO₂, fraction of CO₂ in inspired gas (FiCO₂)
and other parameters were measured in studies characterizing a benefit of AvaLung, a device that removes expired gas from the point of inhalation [8, 9], thus preventing rebreathing of previously expired gas.

During conducting their experiment, Roubik et al. [10] studied, how work of breathing was associated with EtCO₂, FiCO₂, end-tidal concentration of oxygen (EtO₂) and fraction of O₂ in inspired gas (FiO₂) and what was the effect of a snow pocket on these parameters. Furthermore, a threshold EtCO₂ level was used as a primary safety measure for terminating the experimental breathing trial of each volunteer. The authors observed several times, that the value of EtCO₂ on the screen of the monitor changed suddenly and stepwise and that the displayed EtCO₂ value did not correspond to the displayed CO₂ concentration curve. The displayed EtCO₂ value was lower than the expected value according to the measured CO₂ concentration curve. This unexpected behavior of Datex-Ohmeda S/5 life function monitor (Datex-Ohmeda, Madison, WI, USA) has not been docu-mented, to our knowledge.

The aim of the study was to investigate possible errors and their frequency in evaluation of gas parameters (EtCO₂, FiCO₂, EtO₂ and FiO₂) during breathing experiments in the avalanche snow when using Datex-Ohmeda S/5 monitor.

Methods

Study design

The data used in this study were recorded during a prospective randomized double-blind crossover breathing experiment [10]. The study was approved by the Institutional Review Board and registered in the ClinicalTrials.gov registry as NCT02521272. The full protocol of the original study was described in a detail by Roubik et al [10].

Study group

Data recorded in 12 male volunteers were evaluated in this study. The basic characteristics of the group of participants, presented as mean ± standard deviation and range (minimum–maximum), are: age 28.8 ± 3.4 (20–30) years, weight 77.7 ± 7.1 (64–90) kg, height 180.0 ± 5.5 (173–192) cm, BMI—Body Mass Index 24.0 ± 1.7 (20–27) kg∙m^–2, FEV1—Forced Expiratory Volume in 1 second 4.5 ± 0.4 (4.0–5.1) L, and FVC—Forced Vital Capacity 5.2 ± 0.5 (4.5–6.1) L.

Experimental protocol and measurements

Each volunteer underwent two phases of the experiment using a breathing circuit presented in Fig. 1: phase “AP”—breathing in snow with a one-liter air pocket, and phase “NP”—breathing in snow with no air pocket. At least a 20-hour recovery interval was inserted between the two phases in each subject.

The breathing circuit was designed in order to minimize its dead space; therefore, the circuit comprised separate inspiratory and expiratory limbs equipped with one-way valves in order to assure the unidirectional gas flow during inspiration and expiration. The dead space volume of the bidirec-tionally ventilated parts of the tubes was 49 mL.

Before the breathing trial, each subject was con-nected to a mouthpiece allowing measurement of respi-ratory gasses and ventilatory parameters. A stabi-lization period (approx. 5 minutes) for reaching stable ventilatory parameters (steady tidal volume and breathing frequency) was introduced. Then, the subject was connected to the breathing circuit (described above) ending with NP or AP and the breathing trial was initiated. Another stabilization procedure (approx. 5 minutes) followed. This next phase lasted until steady readouts, similar to those recorded before the breathing trial during the stabilization phase, were reached.

Physiological parameters of the subject were recorded by a Datex-Ohmeda S/5 anesthesia monitor (Datex-Ohmeda, Madison, WI, USA) with anesthesia gas module E-CAiOVX (Datex-Ohmeda, Madison, WI, USA) using S/5 Collect software (Datex-Ohmeda, Madison, WI, USA). In this study, a group of parameters were evaluated from the whole set of the recorded parameters. These were all measured at the airway opening and included inspiratory and expiratory curves of O₂ and CO₂ concentrations recorded continuously with a sampling frequency of 25 Hz, inspiratory and end-tidal fractions of oxygen (FiO₂, EtO₂), inspiratory and end-tidal fractions of carbon dioxide (FiCO₂, EtCO₂), tidal volume (V_T), curves of airway pressure (Paw) and airflow (Qaw).

The Datex-Ohmeda S/5 anesthesia monitor, con-nected to a laptop computer for data collection, was placed in a heated tent and thermally stabilized using electric heating foils. The gas sampling lines of the monitor were supplemented with a heated wire and a polyurethane insulation in order to prevent conden-sation and freezing of water in the hoses. The accuracy of the gas analysis module of the Datex-Ohmeda S/5 monitor was checked directly on the site before the first breathing experiment every day using a calibrating gas (5% CO₂, 15% O₂, balanced by N₂) from a high-pressure cylinder.

All details about the preparation of the breathing circuit and snow conditions, safety measures and other details not essential for conducting the current study are presented in the original paper [10].

In order to identify a probable cause of the error, a post hoc bench test was conducted in a lab under better controlled conditions using a model of the snow allowing expired gas rebreathing as depicted in Fig. 2. The model of the snow consisted of a barrel filled with 40 L of moist perlite.

During the post hoc bench test a different patient monitor was used (CareScape B650 GE Healthcare, Helsinki, Finland), which is a successor of Datex-Ohmeda S/5 and uses essentially the same gas measurement technology.

Data processing and statistics

Two sets of data were analyzed and compared: (i) the curves of O₂ and CO₂ and (ii) values of EtCO₂, EtO₂, FiCO₂ and FiO₂ evaluated by the monitor from the curves of O₂ and CO₂. The curves were recorded with a sampling frequency of 25 Hz and the derived parameters were recorded with a sampling rate of 1 Hz. The respective curves and the derived parameters were synchronized and processed in Matlab R2013b soft-ware (MathWorks Natick, Massachusetts, USA).

In the recorded signals, segments corresponding to the breathing trial in snow were selected first (a segment between points ‘B’ and ‘E’ in Fig. 3). The ‘B’ and ‘E’ points were identified as points where rapid changes of gas concentrations occurred as a consequence of connecting and disconnecting of the breathing circuit to the volunteer. This segment, expressed in seconds, represents the total duration of the breathing trial referred to as T_Tot. Then, portions of the signal were the evaluated parameters did not correspond with the respective measured curves, were identified. These erroneous segments are marked with red horizontal abscissas in Fig. 3. Tolerance intervals of ±0.1% CO₂ (abs.) for EtCO₂ and FiCO₂, and ±0.2% O₂ (abs.) for FiO₂ and EtCO₂ were applied around the evaluated trend data during the error detection. The summary duration of all the erroneous segments during the entire breathing trial expressed in seconds is referred to as T_Err. In addition, the total duration of dropouts in the concentration signal were calculated and referred to as T_Drop. These can be seen in Fig. 3. There are 5 dropouts of the signal, where the recorded concentration of both the gases provided by the monitor contains a value of −32 767.

From the determined times T_Tot, T_Err and T_Drop, the percentage of total time when the evaluated parameters are incorrect (Error) and the percentage of time when dropout of the signal is present (Dropout) are calculated according to the following equations:

For statistical evaluation of the results, normality of the data was tested using Kolmogorov-Smirnov test. As the normality of data was violated, non-parametric Mann-Whitney U-test was used for evaluation of statistical significance of the differences between the measured parameters. Statistica 7.1 (StatSoft, Tulsa, OK, USA) was used for statistical calculations and presentation of final data in the form of graphs. P<0.05 was considered as statistically significant.

Results

There were differences in the average durations of erroneous evaluation among EtCO₂, FiCO₂, EtO₂ and FiO₂. These parameters differ also depending on the breathing circuit configuration, i.e. with one-liter air pocket (AP) and without air pocket (NP). These results are summarized graphically in Fig. 4 for oxygen related parameters and in Fig. 5 for carbon dioxide related parameters.

The data presented also demonstrates a significant inter individual variability. As an example, EtCO₂ was evaluated incorrectly in 13% of the total breathing time with AP in one volunteer and in 71% of time in another one. In one volunteer, the error in evaluation of EtO₂ was detected in 93% of the entire breathing trial time with AP. There was not a statically significant difference between the same parameters recorded with AP and NP.

The duration of the dropout in the gas concentration signal was much less in all the conditions (p<0.001), as depicted in Fig. 6. When present, the dropout occurred in both O₂ and CO₂ signals at the same time. The average percentage of the dropout in O₂ and CO₂ measurement during the entire breathing trial was 3.9% for breathing with AP and 3.5% with NP. In several subjects no dropout occurred. The maximum duration of dropout was 10%.

Discussion

The main finding of the study is that Datex-Ohmeda S/5 monitor fails to provide correct values of EtCO₂, FiCO₂, EtO₂ and FiO₂ during experimental breathing in avalanche snow. The error occurs in 30–50% of the entire breathing trial time, but may reach up to 93% in an individual breathing volunteer.

During these breathing experiments, the calibration gas (5% CO₂, 15% O₂, balanced by N₂) was regularly used for verification of the precision of gas concentration measurement. During these calibration procedures, no error in measurement of gas concentrations was identified. The measured values always corresponded to the composition of the calibration gas, even though the verification was conducted in the outside environment as during the breathing experiments.

There was a frequent lack of agreement between concentrations correctly measured by the gas analyzer module of Datex-Ohmeda S/5 and the consequent algorithm calculating EtCO₂, FiCO₂, EtO₂ and FiO₂ values. The algorithm often failed to provide correct values corresponding to the measured O₂ and CO₂ concentrations. Therefore, the cause of the problem may rest in imperfect software.

We never identified a similar error of EtCO₂, FiCO₂, EtO₂ and FiO₂ parameters during preparatory, stabilization or testing phases. The problem occurred during the breathing trial itself and often persisted for a short period of time immediately after the breathing trial (Fig. 3).

The breathing trial phase is characterized by fast changes of the gas concentrations and their trend values, irregular and rapidly changing breathing patterns and breathing parameters outside their normal physiological ranges. Even more, breathing in the snow brings significant accumulation of CO₂ in the snow surrounding the end of the breathing circuit and causes also a decrease of oxygen content in this area. As a consequence, rapidly increasing CO₂ rebreathing and decrease in inspired fraction of oxygen can occur. All these conditions could be related to the failure of the algorithm evaluating EtCO₂, FiCO₂, EtO₂ and FiO₂.

Another possible cause of the problem could be distorted curves of O₂ and CO₂ concentrations due to the breathing circuit used. The scheme of the breathing circuit from Fig. 1 is presented in Fig. 7.

Two limbs of the circuit (inspiratory and expiratory) equipped with one-way valves in order to minimize the dead space during breathing, acting during inspiration and expiration alternatively, result in the gas present in these limbs from the previous breathing cycle being measured first, before the gas from the snow inhalation reached the sensors. This often resulted in concentration curves with two minima and maxima during a single breathing cycle. Further as the composition of gases when breathing with AP and NP differ, different concentration curves occur, as depicted in Fig. 8 and Fig. 9.

In order to verify behavior or the monitor under different conditions, a bench test with the experimental set up depicted in Fig. 2 was conducted. The following conditions were tested: quiet natural breathing, shallow fast breathing, breathing with deep breaths and very irregular breathing. These were all conducted with ambient atmosphere without the model of the snow first. Then the snow model breathing phase was initiated. The resulting concentration curves, evaluated EtO₂, EtCO₂ parameters and other measured breathing parameters are presented in Fig. 10.

Even though the laboratory trial was not conducted with a group of volunteers as a standard study, from the curves presented in Fig. 10 the same behavior of the monitor is apparent as observed during the study during breathing in the real snow. When no rebreathing was present, even with the 2-way breathing circuit, no erroneous evaluations of EtO₂ and EtCO₂ were detected and rapid and significant changes in breathing
pattern did not affect the correctness of EtO₂ and EtCO₂ parameters. The errors occurred during the phase with rebreathing using the model of snow.

The last experiment in the laboratory was conducted using a standard anesthesia machine (Zeus Infi-
nity Empowered, Dräger AG, Lübeck, Germany). A CARESCAPE B650 monitor was used for EtCO₂ monitoring and a separate device, a capnograph (Nellcor OxiMax NPB-75 Nellcor Puritan Bennett, Minneapolis, MN, USA), was used as well. When the standard configuration of the patient circuit with a CO₂ absorber was used, both the monitors performed well even during irregular breathing. During this confi-guration, inspired fraction of CO₂ was always below 1%. Second, the CO₂ absorber in the circuit was emptied, i.e. the absorber did not contain the CO₂ absorbing soda lime. In this configuration, a fast increase in CO₂ concentration in the circuit was recorded similar to breathing in snow or the snow model. Even though the Nellcor OxiMax NPB-75 measured the EtCO₂ correctly, evaluation of EtCO₂ using the CARESCAPE B650 monitor exhibited the same errors as during the breathing experiments in the real snow or in the snow model.

The behavior of the monitor during both the laboratory experiments was very similar to that of during the breathing experiments in the real snow. Neither different nor changing breathing parameters caused the erroneous evaluation of EtO₂ and EtCO₂ when rebreathing of expired gas was not present. The error occurred during the rebreathing and a short period of time immediately after it. But we cannot determine the real cause of the error, as other parameters also varied, with some outside the normal physiological range. For example, airway pressure (Paw) amplitudes were increased markedly due to a high airflow resistance both of the real and simulated snow. On the other hand, the methodology of this article was designed in order to document and quantify the error occurring during the real breathing experiments with human volunteers, not to investigate the exact cause of the problem.

Conclusion

The study documents that even though both the monitors (Datex Ohmeda S/5 and CARESCAPE B650) measured the concentration of gases correctly, the end tidal parameters (EtCO₂, FiCO₂, EtO₂ and FiO₂) were derived incorrectly during breathing in the snow. This condition may represent a possible danger when investigators rely extensively on EtCO₂ parameter during control of the breathing experiments. EtCO₂ is often used for evaluation of safety of the participants, or, as an endpoint of such experiments. Verification of the evaluated parameters, such as EtCO₂, with the corresponding gas concentration curve, should be conducted on a regular basis. For design of prospective research studies, we also recommend recording of concentration waveforms for the consequential verification of provided EtCO₂, FiCO₂, EtO₂ and FiO₂ parameters.

Acknowledgement

The study was supported by grant of Czech Technical University in Prague, grant No. SGS17/203/OHK4/3T/17.

Karel Roubík, Ph.D.

Department of Biomedical Technology

Faculty of Biomedical Engineering

Czech Technical University in Prague

nám. Sítná 3105, CZ-272 01 Kladno

E-mail: roubik@fbmi.cvut.cz

Phone: +420 603 479 901