Article, Emergency Medicine

The effect of the apneic period on the respiratory physiology of patients undergoing intubation in the ED

a b s t r a c t

Objectives: We sought to examine the physiological impact the apneic period has on the respiratory physiology of patients undergoing intubation in the emergency department and whether DAO, the delivery of 15L oxygen by nasal cannula during apnea, can affect the development of respiratory acidosis.

Methods: This was a prospective observational cohort study conducted at an urban academic level 1 trauma cen- ter. A convenience sample of 100 patients was taken. Timed data collection forms were completed during the periintubation period. We report the mean ABG and end-tidal CO2 values between those with normal and prolonged apnea times (N 60 s) and between those who received DAO and those who did not.

Results: 100 patients met our inclusion criteria. There were no significant differences in the pre-RSI ABG values between those who received DAO and those who did not and between those with apnea times less than or N 60 s. Only in the group of patients with apnea times N 60 s did significant changes in respiratory physiology occur. DAO did not alter the trend in respiratory acidosis during the periintubation period. EtCO2 increased as apnea times were prolonged, and DAO altered this trend.

Conclusions: Post-RSI EtCO2 increased as apnea times were prolonged. DAO may alter this trend. Statistically sig- nificant changes in pH and PaCO2 (mean differences of 0.15 and 12.5, respectively) occurred in the group of pa- tients who had mean apnea times of N 60 s but not in those with apnea times b 60 s.

(C) 2017

Introduction

Rapid Sequence Intubation is the preferred method of securing a definitive airway in the emergency department (ED). A great deal of emphasis is placed on optimizing larnygoscopic and intubating condi- tions to avoid hypoxemia [1], which can quickly progress to dangerous- ly low levels during the apneic period. Although there are no studies demonstrating that transient hypoxemia is associated with adverse out- comes in the general ED population, prolonged hypoxemia can poten- tially cause hemodynamic decompensation or brain injury if not addressed [2-5]. In healthy patients, the first minute during the apneic period is thought to increase pCO2 by 8 to 16 mm Hg and then approx- imately 3 mm Hg per minute thereafter [6]. However, little is known about the effect of the apneic period on respiratory physiology during intubation when it is performed as a life-saving measure.

During the apneic period after sedation and Neuromuscular block– ade, the normal pressure gradient between the outside world and the alveoli is absent. Pre-oxygenation alone may be insufficient to prevent Oxygen desaturation, and experts have recommended diffuse apneic

* Corresponding author at: Department of Emergency Medicine, Lincoln Medical and Mental Health Center, 234 E 149th Street, Bronx, NY 10451, USA.

E-mail address: [email protected] (J.R. West).

oxygenation (DAO), the delivery of 15 L oxygen by nasal cannula during apnea, in order to prevent hypoxemia and extend the safe apneic period [1]. Recent studies have shown mixed results on the effect of DAO to lower the incidence of hypoxemia in critically-ill patients undergoing intubation [7-10]. Apneic oxygenation by nasal cannula has been dem- onstrated to delay the onset of hypercarbia in healthy patients undergo- ing elective intubation [11], yet whether DAO can facilitate enough Gas exchange to affect the rate of PaCO2 retention during the peri-intuba- tion period in patients undergoing emergent intubation in the ED has yet to be studied. We sought to examine the physiological impact the apneic period has on PaCO2 retention in patients undergoing RSI in the ED and whether DAO can affect the development of respiratory ac- idosis during the peri-intubation period.

Methods

Study design and setting

This was a prospective observational cohort study conducted at an urban academic level 1 trauma center with an annual census of approx- imately 170,000 patients in New York City from January to April 2016. This institution has an ACGME-accredited 4-year emergency medicine (EM) residency program, and ED intubations are performed by an EM

http://dx.doi.org/10.1016/j.ajem.2017.03.076

0735-6757/(C) 2017

J.R. West et al. / American Journal of Emergency Medicine 35 (2017) 13201323 1321

resident under direct supervision by an EM attending. The residents have extensive training in airway management through a simulation lab, critical care, and anesthesia rotations. The study was approved by the Institutional Review Board. Since a convenience sample of 100 pa- tients was taken, a sample size and power analysis was not performed.

Selection of participants

All adult patients requiring endotracheal intubation were screened for inclusion. Exclusion criteria included patients in cardiac or traumatic arrest, those where awake intubation technique was used, those where pre-oxygenation was not performed, and those where an arterial blood gas was not obtained both prior to and after intubation.

Methods and measurements

An ED intubation timed data collection form was completed for the real-time documentation of the following: indication for intubation, pa- tient demographic data, First pass success rate, oxygen saturations, pre- oxygenation methods, pre-oxygenation time, the use of DAO, and nasal cannula end-tidal CO2 (EtCO2). In addition, the collection form included a measurement of apnea time during the peri-intubation period and the post-intubation EtCO2 measured after confirmation of endotracheal tube placement. This information was collected by an ED provider, an EM resident or attending, assigned to observe and collect data for each intubation. At the time of data acquisition, the collection form was re- corded for a quality improvement database, and the providers were un- aware of our hypothesis. Apnea was confirmed by waveform capnography when the waveform was flat at 0 mm Hg mark. We chose to use 60 s as cutoff for identifying patient with a prolonged apne- ic period, because the rate of PaCO2 rise was previously described as highest during the first minute of apnea [6]. ABGs were collected prior to the RSI process and within 15 min after confirmation of intubation.

Outcomes and analysis

Descriptive statistics were used for demographic data. We compared all ABG and EtCO2 values before and after intubation. Student’s t-test was used for parametric data to compare physiologic variables within the study population. Ninety-five percent confidence intervals (95% CI) and p-values are reported. A p-value of b 0.05 was used to determine significance. We also report the 95% CI of the differences between the means of the pre-RSI and post-RSI ABG and EtCO2 values. We also attempted to correlate apnea time as a continuous variable and plot it against individual first EtCO2 measurements after confirmation of en- dotracheal intubation using a scatter plot. All statistical analysis was perfumed using the Statplus (Analysoft, Walnut, CA) and XLSTAT (Addinsoft, New York, NY) statistical software packages.

Results

A total of 100 patients were enrolled. The average age of the cohort was 56 (95% CI 53.4 to 59.3). Fifty-nine patients were male and 41 were female. A majority of patients were intubated for primary pulmo- nary pathologies. 51 patients received DAO during the study period. The mean SpO2 prior to preoxygenation, preoxygenation time, SpO2 after preoxygenation were 93% (95% CI 91 to 94), 813 s (95% CI 662 to

965), and 98% (95% CI 97 to 96) respectively. The mean apnea time was 65 s (95% CI 57 to 73). We found a first pass success rate of 88%. The median laryngoscopic view based on the Cormack-Lehane classifi- cation system was 1 with an interquartile range (IQR) of 1 to 2. The me- dian American Society of Anesthesiologists (ASA) classification was 2 (IQR 1 to 3). Table 1 demonstrates the patient demographics of the cohort.

Statistically significant, through likely clinically insignificant, chang- es in pH, PaO2, PaCO2, and ETCO2 levels occurred during the peri-

Table 1

Demographics of included patients.

Demographics (n = 100)

95% CI

Past medical history (%)

HTN

48

DM

29

Asthma

15

COPD

12

Cardiac

11

Liver disease

10

Other

19

Indication for intubation (%)

Pulmonary

66

Trauma

13

Neurologic

10

Cardiac

8

Other

3

Abnormal auscultation (%)

65

SpO2 Prior to Pre-Ox (u)

93

91 to 94

Pre-oxygenation time (s)

813

662 to 965

SpO2 After Pre-Ox (u)

98

97 to 99

Apnea time (s)

65

57 to 73

First pass success rate (%)

88

SpO2 after confirmation (u)

99

98 to 99

Abbreviations: HTN, hypertension; DM, diabetes; COPD, chronic obstructive pulmonary disease; SpO2, peripheral oxygen saturation; Pre-ox, preoxygenation.

intubation period. The mean ABG values before and after the intubation are demonstrated in Table 2. The differences between the pre-RSI and post-RSI means of the pH, PaO2, PaCO2, and EtCO2 levels were 0.05 (95% CI 0.01 to 0.09), 174.5 (95% CI 138.5 to 10), 11.5 (95% CI 2.5 to

20.5), and 8.7 (95% CI 5.3 to 11.7), respectively. In 48 patients, the apnea time exceeded 60 s. Differences in the fall in pH and rise of PaCO2 levels occurred in this group as compared to the 52 patients with apnea times b 60 s. In patients with prolonged apnea times, the dif- ferences between the means of the pH and PaCO2 levels were 0.15 (95% CI 0.11 to 0.18) and 12.5 (95% CI 4.5 to 29.5), respectively. In compari- son, the differences between the mean pH and PaCO2 levels of patients with apnea times b 60 s were 0.05 (95% CI 0 to 0.1) and 6.2 (95% CI 2.1 to 14.5). Table 3 demonstrates the differences in ABG and EtCO2 values be- tween those patients who received DAO during RSI and those that did not among the 48 patients with apnea times N 60 s. The Fig. 1 shows the scatter plot of first EtCO2 measured after confirmation of endotra- cheal intubation versus apnea time, and the linear regression trend line showed a positive correlation for those not receiving DAO and neg- ative correlation for those who received DAO.

Table 2

Mean arterial blood gas analysis values and end-tidal CO2 before and after intubation.

Variable

Pre-RSI

Post-RSI

Difference

95% CI

p-Value

All patients

n = 100

n = 100

pH

7.29

7.24

– 0.05

0.01-0.09

0.035

aO2

71.5

246

174.5

138.5-210

0.001

aCO2

43.9

55.4

11.5

2.5-20.5

0.04

Bicarb

22.2

27.1

4.9

1.9-11.7

0.3

EtCO2

28.8

37.5

8.7

5.3-11.7

0.001

SpO2

97.4

95.7

– 1.7

0.7-4.1

0.072

Apnea time b 60s

n = 52

n = 52

pH

7.49

7.44

– 0.05

0-0.1

0.42

aO2

69

225

156

107-205

0.001

aCO2

42.3

48.5

6.2

2.1-14.5

0.16

EtCO2

29

36.9

7.9

3.6-12.2

0.005

SpO2

98

97

– 1

0.7-2.7

0.44

Apnea time N 60s

n = 48

n = 48

pH

7.5

7.35

– 0.15

0.11-0.18

0.023

aO2

73

265

192

138-246

0.001

aCO2

47

59.5

12.5

4.5-29.5

0.014

EtCO2

28

38

10

2-18

0.001

SpO2

97

94

– 3

0.6-6.6

0.09

1322 J.R. West et al. / American Journal of Emergency Medicine 35 (2017) 13201323

Table 3

Mean arterial blood gas analysis values and end-tidal CO2 between those who received DAO and had prolonged apnea times.

No DAO (n = 25) DAO (n = 23)

Variable

Pre-RSI

Post-RSI

Difference

95% CI

p-Value

Pre-RSI

Post-RSI

Difference

95% CI

p-Value

pH

7.28

7.24

– 0.04

0.01-0.07

0.1

7.3

7.24

– 0.06

0.03-0.09

0.02

aO2

79

248

169

129-209

0.001

92.8

248

155.2

110-200

0.0001

aCO2

46

54

8

1-15

0.08

45

60

15

2-28

0.08

EtCO2

29.5

38.4

8.9

4.8-13

0.0001

26

34.5

8.5

3.5-13.5

0.0001

SpO2

98.3

95.8

– 2.5

0.1-4.6

0.04

96.6

94

-2.6

0.2-4.7

0.09

Discussion

To our knowledge, no study has reported the relationship between apnea time and respiratory acidosis among critically ill emergency de- partment patients requiring RSI. The most important finding of this study was that end-tidal CO2 increases as the apneic period is prolonged. During the peri-intubation period, we report our cohort had statistically significant, though likely of low clinical significance, changes in pH and PaCO2. We report a mean apnea time of just over one minute. We report no substantial changes in pH and PaCO2 in the group with apnea times b 60 s, though PaCO2 increased by 6 mm Hg in this group. Only in the group whose mean apnea time was N 60 s did statistically significant changes in respiratory physiology occur. It is important to note that the clinical significance of our findings is likely insignificant for most patients requiring intubation. However, this find- ing may be of great importance when intubating a patient with severe metabolic acidosis, since post-RSI inadequate ventilation has been shown to be associated with clinical deterioration in at least a subgroup of these patients [12]. Our limited exclusion criteria enhance the gener- alizability of these findings in patients who have an ABG drawn prior to intubation. We believe our inclusion criterion of an ABG prior to intuba- tion may represent a patient population whose illness did not warrant immediate intubation upon Initial resuscitation.

The factors affecting safe apnea time have been discussed in the an- esthesia literature since the emergence of endotracheal intubation. Re- cent expert recommendations have suggested the delivery of 15 L O2 by nasal cannula during the apneic period until the endotracheal tube is secured [1]. Apneic oxygenation during emergency intubation has been studied in the pre-hospital [10], ED [7,8], and critical care [9] set- tings, and all have focused on the incidence of hypoxia or first endotra- cheal tube pass without hypoxia. This is the first study of the effect of apneic oxygenation by nasal cannula on the respiratory physiology of emergency department patients undergoing RSI. In patients receiving DAO, we found a negative correlation between EtCO2 measured after confirmation of intubation and apnea time. This suggests DAO may facil- itate gas exchange and reduce the degree of respiratory acidosis in

patients with prolonged apneic periods. Previously, the effect of apneic oxygenation on the respiratory physiology of healthy patients undergo- ing elective intubation demonstrated that DAO may facilitate gas ex- change and prolong the onset of respiratory acidosis in patients with prolonged apnea [11]. The author of this study used standardized arte- rial blood gas times, and it was not feasible for us to standardize our blood gas measurement times in the setting of acute critical illness. The presence or absence of DAO in our study did not support this trend in respiratory acidosis when measured by blood gas analysis be- fore and within 15 after intubation.

Our study is not without limitations. Numerous providers collected the data, though each data collector was an ED provider only assigned the role of data collection during RSI using a timed and standardized form. We avoided self-reporting, because clinicians are known to under-report adverse events [13] and the time to intubation [14]. Al- though all post-intubation blood gas analyses were performed within 15 min of confirming intubation, we were unable to ascertain whether the timing of second blood gas may have influenced our data. It is rea- sonable to assume that most of the respiratory acidosis during the apne- ic period would have been corrected by post-intubation ventilation, and the lack of standardization of the second blood gas is a significant limi- tation. Additionally, including only patients with a pre-intubation blood gas may have caused us to exclude the most critically ill patients.

Unidentified cofounders such as pulmonary function status, obesity, and other predictors of difficult airway may have affected our results. We also did not perform a subgroup analysis of patients who may have been most likely to benefit from DAO, such as those with hypox- emic or hypercarbic respiratory failure or those with severe underlying metabolic acidosis. Furthermore, we were unable to account for the rates of post-intubation bagging or mechanical ventilation settings, which may have affected our results.

Conclusion

In patients undergoing RSI in the ED, we found that post-RSI end- tidal CO2 increased as apnea times were prolonged. Diffuse apneic

Fig. 1. Scatter plot of first end-tidal CO2 measured after intubation versus apnea times.

J.R. West et al. / American Journal of Emergency Medicine 35 (2017) 13201323 1323

oxygenation may reduce this trend. Statistically significant changes in pH and PaCO2 (mean differences of 0.15 and 12.5, respectively) oc- curred in the group of patients who had mean apnea times of N 60 s but not in those with apnea times b 60 s. Prospective trials are necessary to evaluate the effect of these findings on patient outcomes.

Author contributions

NDC conceived and designed the study. JRW, AS, CK analyzed the lit- erature. NDC analyzed the data. JRW, AS, CK, and NDC drafted the man- uscript; and all authors contributed substantially to its revision. JRW takes responsibility for the paper as a whole.

Conflict of interest

JRW, AS, CK, and NDC declare no conflicts of interest.

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