TITLE: 
Apneic Oxygenation during simulated prolonged difficult laryngoscopy: Comparison of nasal prongs versus nasopharyngeal catheter: A prospective randomized controlled study



ABSTRACT.BACKGROUND:
Apneic oxygenation by insufflating O2 through nasal prongs (NP) and nasopharyngeal catheter (NC) has been proven to be effective. We conducted this study to compare the relative efficacy of these two techniques in a simulated difficult airway situation.

ABSTRACT.OBJECTIVE:
The objective of this study is to evaluate the influence of two techniques of apneic oxygenation (NP vs. NC) on the duration of oxygen saturation ≥95% during simulated prolonged difficult laryngoscopy.

ABSTRACT.METHODS:
A randomized non-blinded study was conducted in 56 adult patients, 28 in each group belonging to American Society of Anesthesiologists physical status class I and II scheduled for elective surgical procedures under general endotracheal anesthesia randomized to either NC or NP group. After pre-oxygenating for an end tidal oxygen concentration of 90% and induction, ability to mask ventilate was checked and paralyzed with rocuronium. Apneic oxygenation using 5 L/min of O2 was established either by NP or NC. After laryngoscopy the laryngoscope was withdrawn to simulate a Grade 4 laryngoscopy and held in this position for an apnea time (T1) of 10 min with SpO2 maintained at ≥95% or until SpO2 dropped to < 95%, whichever is earlier. An arterial blood gas analysis was performed at the end of T1. Desaturation to < 95% were compared between the groups using Chi-square test (P < 0.05 as significant). Arterial blood gas analysis among those who sustained T1 for 10 min between the groups were compared using independent sample t-test (P < 0.05 was considered as significant). None of patients were excluded from the study.

ABSTRACT.RESULTS:
In NP group nine patients desaturated as against none in the NC group (P = 0.001). Arterial blood gas analysis among non-desaturated patients was comparable with respect to PO2, PCO2 and pH.

ABSTRACT.CONCLUSION:
Nasopharyngeal catheter is a better device than nasal prongs in maintaining safe oxygenation during apnea in a simulated prolonged difficult laryngoscopy.

BODY.INTRODUCTION:
The physiologic phenomenon of apneic oxygenation has been exploited appropriately in difficult airway situation wherein, apneic mass movement of oxygen can easily be achieved by adequate pre-oxygenation followed by insufflation of oxygen using different techniques, thereby preventing patient desaturation and extending the period of safe apnea time.[1]
Of these various techniques, oxygen insufflation using nasal prongs (NP) and nasopharyngeal catheter (NC) has been proven to be effective.[2345] We conducted this randomized controlled study to compare the relative efficacy of oxygen insufflation with these two techniques during apneic oxygenation in a simulated difficult airway situation.

BODY.OBJECTIVE:
The objective of this study was to evaluate the influence of two techniques of apneic oxygenation (NP vs. NC) on the duration of oxygen saturation ≥95% during simulated prolonged difficult laryngoscopy.

BODY.METHODS:
This prospective randomized non-blinded study was commenced after obtaining approval from the Departmental Dissertation Committee, Institutional Ethics Committee and written informed consent from patients. A safety report was also submitted to the Ethics Committee after conducting the initial round of cases. Patients of either gender aged between 18 and 55 years belonging to American Society of Anesthesiologists I or II, scheduled for elective surgery under general anesthesia requiring orotracheal intubation were included. Exclusion criteria were - body mass index (BMI) <18 and ≥30 kg/m²; patients having nasal obstruction or history of epistaxis; patients with anticipated difficult airway; patients having present or past history of difficult mask ventilation; patients having present Grade 3a/3b or 4 laryngoscopy view (Yentis and Lee's modification of Cormack and Lehane); patients having chronic obstructive pulmonary disease, reactive airway or parenchymal disease.
Patients were randomly allocated using a computer generated table of random numbers under two groups:

Group NC
Group NP


Two observers participated in the study and their roles were defined as follows:

Observer 1: Who did the pre-operative evaluation, post-operative assessment, recording of measurements intra-operatively and took the arterial blood sampling
Observer 2: Who performed the pre-oxygenation, application of appropriate insufflation device, laryngoscopy and intubation.


Blinding was not possible because of hissing sound created while insufflation of O2 through the NC.
Preoperatively, all patients were kept nil per oral as per standard fasting guidelines. Premedicated with intravenous (IV) midazolam 0.02 mg/kg in the operation room. Pre-induction monitors included a 5-electrode electrocardiogram, non-invasive blood pressure, pulse oximeter, entropy, end tidal oxygen and carbon dioxide concentration using Datex-Ohmeda 5/5™ anesthesia work station monitor. An additional monitor (Life Sense® LS1-pR med-air) was also used for monitoring SpO2. Nasal patency was checked in all patients using Life Sense® monitor. Observer 2 started pre-oxygenation by deep breathing technique using a tight fitting face mask through circle absorber system at a fresh gas flow of 10 L/min of O2 and was continued until the end-tidal oxygen concentration (ETO2) reached 90%. Patient was induced with IV fentanyl 2 μg/kg and IV propofol (Claris™) 2.5 mg/kg. After patient was unresponsive, ability to mask ventilate was checked followed by the introduction of the respective insufflation device connected to oxygen source at a flow rate of 5 L/min. Once the face mask was taken off, a stop watch was started for noting apnea time (T1). Patient was paralyzed with IV rocuronium 1 mg/kg. Propofol infusion was started at 150 μg/kg/min and was titrated to maintain state entropy value between 40 and 60 throughout the study period. After 60 s of injecting rocuronium, observer 2 proceeded with laryngoscopy. Laryngoscopy was graded without optimal external laryngeal manipulation and if Grade 3a/3b or 4 was seen, patient was excluded from the study. Once Grade 1 or 2a/2b was confirmed, the observer 2 proceeded to a simulated difficult laryngoscopy by withdrawing the laryngoscope blade to achieve a Grade 4 view. The laryngoscope was kept in this position until SpO2 fell to <95% or T1 of 10 min had elapsed, whichever was earlier. An arterial blood sample was taken at the end of T1. After intubation, intermittent positive pressure ventilation (IPPV) was started with a fresh gas flow of 5 L/min of oxygen delivered through the circle absorber system with a tidal volume of 10 mL/kg and a respiratory rate of 12 breaths per minute set in the ventilator. Maximum ETCO2 value registered in the monitor was noted as IPPV continued. Resaturation time (T2) defined as the time interval from the beginning of positive pressure ventilation until SpO2 reached the maximum value, was also noted. Serial measurements of heart rate, blood pressure and SpO2 were recorded every minute during the entire study period. During laryngoscopy, evidence of bleeding if any was noted. Postoperatively patients were assessed for awareness using Modified Brice Interview, once patient was fully awake, conscious and well oriented.[6]
In group NP, after checking for the ability to mask ventilate, patients were connected to the NP (Airway® surgical Ltd.) attached to the common gas outlet and insufflated with oxygen at a flow rate of 5 L/min. Whereas in group NC, both the nares were prepared prior to induction with oxymetazoline 0.05% nasal drops and after checking for the ability to mask ventilate, a 12 F NC (Polymed®) lubricated with an inert jelly was inserted through the nares within 10 s which in turn was attached to the common gas outlet through an oxygen tubing. Distance between the nares to the tragus of the ear was measured as a rough guide for the depth of insertion of the catheter and oxygen was insufflated at a flow rate of 5 L/min.
BODY.MODIFIED BRICE INTERVIEW FOR POST-OPERATIVE ASSESSMENT OF AWARENESS:
Consists of five questions that were asked to patient once they were fully awake, conscious and well-oriented.[6]

What was the last thing you remember before surgery?
What was the first thing you remember once you woke up?
Did you have any dreams while you were asleep for surgery?
What was the worst thing about your operation?
Did you have any problems going to sleep?


Based on the pilot study of 10 cases (5 cases in each group) showing a difference of 0.75 min of safe apnea time between the two groups, for a power of 80%, a sample size of 28 in each group was required at 95% confidence level. Statistical analysis of the data was performed using SPSS version 18.0 for Windows (SPSS Inc. Chicago, IL., USA).
Continuous variables such as age, weight, BMI, arterial blood gas values were analyzed using independent sample t-test. Chi-square test was used to analyze gender and desaturation between the groups. Fisher's exact test was used for analyzing laryngoscopy grades.


BODY.RESULTS:
A total of 56 adult patients were studied, 28 in each group. All patients were included for statistical analysis. Patient characteristics are given in Table 1. The two groups were comparable with respect to distribution of age, weight and BMI.
Table 1Patient Characteristics
In the Group NP, 32% of patients desaturated [Table 2] against none in Group NC (P = 0.001).
Table 2Desaturation among the two groups
The grades of laryngoscopy [Table 3] between the two groups are also comparable (P = 0.104). Among nine patients who desaturated in Group NP, the laryngoscopy grades were equally distributed – three patients each in Grade 1, 2a and 2b. Table 4 shows the time range of the nine patients who desaturated in Group NP. The apnea time ranged between 6 min 4 s and 9 min 47 s among those who desaturated to a SpO2 of <95%. The time taken to resaturate (T2) from the lowest SpO2 to the baseline value was in the range of 15-90 s.
Table 3Laryngoscopy grades in both groups
Table 4T1 &T2 of the desaturated patients
In Table 5, only the non desaturated patients are analyzed. The pH, PaCO2 and PaO2 were comparable among both groups. The same is represented in terms of range in Table 6. Among the 9 patients who desaturated, the mean pH was 7.27 with a mean PaCO2 of 55.3 mmHg. The mean PaO2 was 75.43 mmHg. The lowest SpO2 recorded among these patients was 91%.
Table 5Arterial blood gas analysis among the non-desaturated patients
Table 6Range of the arterial blood gas values among the non-desaturated patients
Six patients in the Group NP and 4 patients in the group NC needed treatment with IV mephentermine when systolic blood pressure fell to <20% of baseline. One patient in each group required treatment with IV glycopyrrolate 0.2 mg when the heart rate fell to <50 bpm. Eight patients in the Group NC had evidence of minimal bleeding in the pharynx observed during laryngoscopy. Modified Brice Interview did not reveal any evidence of awareness during the study period or surgery.

BODY.DISCUSSION:
Our routine day-to-day pre-anesthetic check-up aims to prepare patient for safe anesthesia. Despite all precautions, there have been instances when difficult airway presents unexpectedly. However, if we continue to give oxygen by some means, the safe apnea time can be prolonged. Hence, we wanted to evaluate whether oxygen devices, which are readily available in the operation room can be used in an unanticipated difficult airway to prevent arterial desaturation whilst equipment or personnel for tackling the difficult airway are being arranged. Hence we conducted this randomized controlled study, to compare the effectiveness of the two devices – NP and NC with respect to the duration of saturation ≥95% during apneic oxygenation in a simulated prolonged difficult laryngoscopy.
We have followed deep breathing technique of pre-oxygenation with a fresh gas flow of 10 L/min, with an objective end point of ETO2 reaching 90%. Irrespective of the technique of pre-oxygenation, the end points of maximal alveolar oxygenation or denitrogenation have been defined as an ETO2 of approximately 90% and an end tidal nitrogen concentration of 5%.[7]
A single positive pressure breath delivered to confirm mask ventilation before paralyzing the patients could have added on to the effect of pre-oxygenation on safe apnea time. For the same reason, apnea time was extended to 10 min to study the influence of apneic oxygenation over and above that of pre-oxygenation. During apneic oxygenation, hypercarbia is unavoidable. To study the partial pressure of blood gases we did an arterial blood gas analysis at the end of the study period T1. However, there is little agreement as to what constitutes a “toxic” level of carbon dioxide.[1]
To prevent awareness propofol infusion was considered and entropy was monitored to titrate the infusion. To add to safety measures, we used an additional SpO2 monitor (Life Sense® monitor) with a rapid response time of 6 s for monitoring the arterial saturation.
In this study, we found that oxygen insufflation through NC is better than the NP in a stimulated prolonged difficult laryngoscopy [Table 2] in terms of maintaining safe oxygenation. The reason is that the NC is placed more nearer to the trachea than the NP and therefore oxygen is delivered more effectively to the trachea, whereas in case of the NP the oxygen may get dissipated to the atmosphere if not properly positioned, if nasal patency is inadequate or upper airway obstruction is present anywhere down the tract. During simulated difficult laryngoscopy upper airway patency could be lost at the pharyngeal level by the soft-tissues, pharyngeal muscles and base of the tongue. In this regard, the NC can successfully circumvent this problem.[234]
Ramachandran et al. studied the influence of nasal oxygen administration on the duration of arterial oxygen saturation (SpO2) ≥95% during simulated difficult laryngoscopy in obese patients.[5] None of patients who received nasal oxygen desaturated to < 95% in 6 min of apnea time. Patients were paralyzed with succinylcholine (Sch) and were kept apneic for 6 min. Sch can act for duration of 5-10 min and recovery characteristics might vary from patient to patient. To overcome this possibility, we have used rocuronium at a dose of 1 mg/kg. Taha et al. conducted a study to evaluate the effectiveness of nasopharyngeal oxygen insufflation following pre-oxygenation using the four deep breath technique within 30 s, on the onset desaturation during the subsequent apnea for 6 min.[2] It was found that in the study group SpO2 was maintained in all patients at 100% throughout the 6 min of apnea compared to none in the control group. Assuring the patency of the upper airway was not addressed.
A randomized controlled trial conducted by Baraka et al., morbidly obese patients received nasopharyngeal oxygen supplementation following pre-oxygenation versus pre-oxygenation alone.[3] Time from the onset of apnea until SpO2 fell to 95% was compared between the two groups with a cut off of 4 min. In the control group, the SpO2 fell from 100% to 95% much faster with a significantly negative correlation between the time to desaturation and BMI. In the study group, the SpO2 was maintained in 16 of 17 patients at 100% for 4 min. However, they did not comment on not maintaining the patency of upper airway while oxygen insufflation. In a cross over study conducted by Teller et al. it was found that during pharyngeal insufflation of oxygen, SaO2 never fell below 97% during the entire 10 min of apnea in any subject.[4] Conversely, when the same group of patients were subjected to apnea in the absence of oxygen insufflation, the duration of apnea was significantly reduced. Patency of the upper airway did not receive any attention in their study. Fraioli et al. conducted a study on apneic oxygenation with a pharyngeal catheter for oxygen administration versus patients undergoing minor procedures with a cuffed endotracheal tube in place for oxygen administration.[8] They found that the majority of patients tolerated apneic oxygenation for 15 min or longer, however, few patients could not tolerate apneic oxygenation for more than 5 min. The fall in oxygen saturation in these patients was attributed to patients relatively smaller predicted Functional Residual Capacity weight ratio. Heller et al. were the first to measure PaO2 in six apneic patients.[9] When the endotracheal tube was left open to room air during apnea, hypoxia occurred within 5 min. When the endotracheal tube was connected to a reservoir of 100% oxygen, PaO2 was about 400 torr after 5 min, but about 100 torr less than it had been at the start of apnea. They stated that accumulating alveolar carbon dioxide and nitrogen can account for only a slight decline in PaO2 and that other factors were also operative in determining the total decrease in PaO2. They postulated changes in pulmonary ventilation-perfusion ratios as an additional factor. However, in our study pre-test PaO2 was not measured to observe the similar change. Frumin et al. conducted a study on eight patients in whom apneic oxygenation was conducted for 15-55 min. Here, the SpO2 never fell below 98%.[1] However, arterial blood gas analysis showed raised PaCO2 levels of 130-160 mmHg and pH was 6.72-6.92. In our study, taking the duration of apnea into consideration, the arterial blood gas values were within acceptable limits [Tables 5 and 6] and also an expected CO2 build up was not observed because of deep breathing technique of pre-oxygenation wherein the ETCO2 had dropped to <30 mmHg in all patients by the time ETO2 reached 90%. After initiating positive pressure ventilation, the ETCO2 returned to normal values within few minutes. Authors also observed a moderate to severe arterial hypertension followed by a mild hypotension when artificial respiration was resumed. They attributed this finding to increasing circulating levels of catecholamines. In our study, 6 patients in Group NP and four patients in Group NC needed treatment with IV mephentermine. The range of PaCO2 levels in those who have tolerated apnea for 10 min ranged between 49.7 and 76.72 mmHg [Table 6]. No evidence of the effects of hypercarbia such as systemic hypertension, tachycardia or arrhythmia was noted.
To conclude, nasopharyngeal catheter is a better device than nasal prongs in maintaining safe oxygenation during apnea in a difficult prolonged laryngoscopy, especially when the patency of the upper airway is not assured. Applicability of our technique in real difficult airway situation requires further evaluation. Comparison of pre-test and the post-test arterial blood gas values would have been more informative. Despite all the necessary precautions, there is no fool proof method to know if the laryngoscope was maintained in the same position and whether the upper airway was kept patent throughout the study period.

Question: Compared to nasopharyngeal catheter (NC) what was the result of nasal prongs (NP) on The grades of laryngoscopy?
Evidence: In the Group NP, 32% of patients desaturated [Table 2] against none in Group NC (P = 0.001).
Answer: no significant difference