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Low-positive pressure ventilation improves non-hypoxaemic apnoea tolerance during ear, nose and throat pan-endoscopy

A randomised controlled trial

Abou Arab, Osama; Guinot, Pierre-Grégoire; Dimov, Evgeny; Diouf, Momar; de Broca, Bruno; Biet, Aurélie; Zaatar, Rody; Bernard, Eugénie; Dupont, Hervé; Lorne, Emmanuel

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European Journal of Anaesthesiology: April 2016 - Volume 33 - Issue 4 - p 269-274
doi: 10.1097/EJA.0000000000000394
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General anaesthesia always requires pre-oxygenation to boost the body's oxygen reserves and thus, increase the safety of induction and tracheal intubation.1 Several methods of pre-oxygenation have been described, assessed and validated.2–6 At present, spontaneous ventilation for 3 to 5 min is the most frequently used and recommended method for the general population.7 However, several studies have demonstrated that pre-oxygenation during spontaneous ventilation is often ineffective and that up to 50% of patients may experience hypoxaemia during induction.8,9 It has been suggested that pressure support ventilation (PSV) using positive end-expiratory pressure (PEEP) with or without positive inspiratory pressure (PIP) may be better than spontaneous ventilation for pre-oxygenation of patients at risk of desaturation and/or hypoxaemia (e.g. obese, pregnant or intensive care patients).10–13 However, no previous study has evaluated this method in a general population who do not have predictable risk factors for hypoxaemia.

In ear, nose and throat (ENT) surgery, pan-endoscopy performed under general anaesthesia is frequently associated with hypoxaemia. At present, there are no guidelines on management of the upper airway for ENT pan-endoscopy.14 Several methods have been described but none has yet prevailed in clinical practice.14–17 The most frequently reported technique is high-frequency jet ventilation, which is associated with low but non-negligible incidences of morbidity (emphysema, pneumothorax and pneumomediastinum).14,15 In the knowledge that PSV can improve the quality of pre-oxygenation and in the absence of a validated ‘gold standard’ method for use before ENT pan-endoscopy, we sought to determine whether or not pre-oxygenation with PSV increases the duration of non-hypoxaemic apnoea in non-obese patients.


Ethical approval for this study (Ethical Committee 2012-A01053–40) was provided by the Comité de Protection des Personnes Nord-Ouest II CHU – Place V. Pauchet, 80054 AMIENS Cedex 1 (Chairperson Bou Pierre) on 15 January 2013. The first patient was recruited on 19 September 2013. As the study was accepted as ‘Soins courants’ (routine care), all patients received written information and gave their verbal consent to participation. Written consent was not required. Development of the study was at Délégation à la recherche Clinique et à l’innovation, CHU Nord, Amiens.

A controlled, open, randomised superiority study was conducted in Amiens University Hospital. Consecutive adult patients aged 18 years or over scheduled for ENT pan-endoscopy were considered for inclusion. The main exclusion criteria were acute respiratory failure, obstructive sleep apnoea, BMI > 35 kg m−2, home oxygen therapy, tracheostomy and guardianship. Randomisation was performed using dedicated software.

In the operating room, the patient's ECG, peripheral capillary oxygen saturation (SpO2) and blood pressure were monitored continuously. The included patients were randomised 1 : 1. Patients in the control arm continued spontaneous ventilation at neutral pressure, with a gas flow rate of 10 l min−1 and an inspired oxygen fraction (FIO2) of 1. In the interventional arm, PSV was performed with a PIP of 4 cmH20, PEEP of 4 cmH2O, a trigger of 1 l min−1, a gas flow rate of 10 l min−1 and an FIO2 of 1. Pre-oxygenation was considered to be successful when the end-tidal oxygen concentration (EtO2) was over 90%. If pre-oxygenation was unsuccessful, the lungs were oxygenated manually for 10 min. The fresh oxygen gas was delivered by a mechanical ventilator (Dräger Medical SAS, Luebeck, Germany) in all patients included in the study.

On arrival in the operating room, the patient's demographic and haemodynamic data were noted (age, weight, height, sex, American Society of Anesthesiologists’ physical status, Mallampati score, the presence of a beard or moustache, dental state, co-morbidities, preoperative haemoglobin concentration, blood pressure, heart rate and SpO2). Haemodynamic and respiratory data (ventilation rate, exhaled tidal volume, exhaled end-tidal carbon dioxide concentration and the presence of leak) were also recorded 2 min after the start of pre-oxygenation and after the onset of apnoea. The times at which SpO2 reached 98, 96, 94, 92 and 90% during the pan-endoscopy session were noted. The duration of non-hypoxaemic apnoea was defined as the time between withdrawal of the face mask and the moment when SpO2 fell to 90%. The duration of pre-oxygenation was defined as the time between placement of the face mask and the moment when EtO2 exceeded 90%. The tolerability of pre-oxygenation was graded by the patient in the recovery room on a 4-point scale (grade 1, very good; grade 2, good; grade 3, average; grade 4, very poor).

General anaesthesia was standardised and comprised pre-medication with oral hydroxyzine 1 mg kg−1, intravenous induction with propofol 3 mg kg−1 and alfentanil 20 μg kg−1, and maintenance by intermittent bolus doses of propofol, as determined freely by the attending anaesthetist. The objective was to maintain apnoea throughout the pan-endoscopy session. Two anaesthesiologists were present: one stood near the patient's head and managed the oxygenation and ventilation, and the other was responsible for induction. Pre-oxygenation was continued during induction of anaesthesia until apnoea occurred. Pan-endoscopy was initiated once apnoea had occurred. If SpO2 fell below 90%, the study was interrupted and manual ventilation with an FIO2 of 1 was performed until SpO2 reached 100%.

The primary efficacy criterion was the duration of non-hypoxaemic apnoea (i.e. before the SpO2 decreased to 90%). Secondary outcomes were kinetics of desaturation, duration of pre-oxygenation, pre-oxygenation failure and tolerance.


We performed a pilot study involving 12 patients which showed a mean time of non-hypoxaemic apnoea of 414 (95% CI 271 to 558) s in the PSV group and 278 (CI 158 to 398) s in the spontaneous ventilation group. A sample size of 50 would be enough to demonstrate a difference in the duration of non-hypoxaemic apnoea of more than 95 s with a power of 80% and an alpha risk of 5%. The distributions of variables were assessed using a Kolmogorov–Smirnov test. Data were expressed as proportion (%), mean (SD) or median (interquartile range), as appropriate. The non-parametric Mann–Whitney test, Wilcoxon test, or Fisher's exact test were applied, as appropriate. The primary end point was also evaluated with a mixed model analysis of variance after adjustment for sex ratio and baseline SpO2 by using natural logarithmic transformation. The threshold for statistical significance was set to P < 0.05. All statistical analyses were performed with R software (version 3.0.1).


During the study period, 67 patients had pan-endoscopy with general anaesthesia. Of these patients, 17 were excluded: three patients had a tracheostomy; four patients had guardianship; and for 10 patients the ventilator was undergoing maintenance. Finally, 50 consecutive patients were included in the study (Fig. 1). The demographic characteristics of the groups were similar, with the exception of a lower proportion of females, a higher SpO2 and a greater proportion of patients with tooth loss in the PSV group (Tables 1 and 2). After 2 min of pre-oxygenation, patients in the PSV group had a higher exhaled tidal volume than those in the control group (Table 2). At the onset of apnoea, none of the haemodynamic and pre-oxygenation parameters differed between the two groups (Table 2).

Fig. 1
Fig. 1:
Study flow chart.
Table 1
Table 1:
Characteristics of the study participants at baseline
Table 2
Table 2:
Ventilatory and haemodynamic variables at baseline, after 2 min of pre-oxygenation and at onset of apnoea

None of the patients resumed spontaneous ventilation during the examination. The duration of non-hypoxaemic apnoea was significantly longer in the PSV group than in the control group [598 (447 to 717) s vs. 310 (217 to 451) s], respectively; P < 0.0001) (Table 3). After adjusting for sex and baseline SpO2, the duration of non-hypoxaemic apnoea remained significantly longer in the PSV group (P = 0.0008). Desaturation was also slower in the PSV group and the time to reach each SpO2 step was longer in the control group (P < 0.05).

Table 3
Table 3:
Time points (s) for each 2% decrease in peripheral capillary oxygen saturation

Pre-oxygenation failed (i.e. EtO2 < 90%) in five patients (20%) in the control group but was successful in all patients in the PSV group. The duration to reach an EtO2 over 90% (successful pre-oxygenation) was shorter in the PSV group than in the control group (Table 2). There was no significance intergroup difference in the duration of pan-endoscopy [393 (305 to 550) s in the PSV group and 330 (262 to 485) s in the control group] (P = 0.252). Fifteen patients (60%) in the control group required manual ventilation, whereas this was required in only two patients (8%) in the PSV group (P < 0.05). The patients in the control group tolerated oxygenation better than those in the PSV group (grade 1, n = 22; grade 2, n = 3 compared with grade 1, n = 16; grade 2, n = 9 in the control group) (P = 0.04). None of the patients in the study graded the tolerability as poor (grade 3) or very poor (grade 4).


This study demonstrated that oxygenation with PSV was associated with a longer duration of non-hypoxaemic apnoea during pan-endoscopy (a median of 6 min, compared with a median of 3 min in the control group) and a less frequent need for manual ventilation. Furthermore, the time course of pre-oxygenation and the decrease in SpO2 were slower in the PSV group.

Anaesthesia has become significantly safer over the last 50 years.17 Nevertheless, there is still a need for better pre-oxygenation. Indeed, a recently published study showed that pre-oxygenation failed in 56% of patients despite the use of recommended methods.9 The primary result reported by this study was an increase in duration of non-hypoxaemic apnoea. Several studies have previously demonstrated that PSV can improve oxygenation and duration of non-hypoxaemic apnoea in populations at increased risk of hypoxaemia.10–12 Our study demonstrated these effects even in a general population without a predictable risk of hypoxaemia. Our results also confirm the study of Tanoubi et al.,13 which demonstrated a significantly shorter pre-oxygenation time with PSV. It should be noted that most patients included in the present study had more than one risk factor for difficult ventilation: age over 55 years; male gender; American Society of Anesthesiologists’ physical status > 2; and a beard or moustache.9 Moreover, the proportion of patients with tooth loss was higher in the PSV group. Despite this, all patients achieved successful pre-oxygenation (EtO2 > 90%) in that group. No study has previously focused on associations between risk factors of ventilation failure and pre-oxygenation mode. The use of PSV may have circumvented risk factors of ventilation failure in these patients. Although the tolerability of pre-oxygenation was better in the control group, none of the patients in the PSV group experienced pain or graded the tolerability as poor or very poor (grade 3 or 4). Equally, no negative cardiovascular effects were noted in the PSV group. Thus, in clinical practice, pre-oxygenation using PSV should be used as a standard of care because it can improve pre-oxygenation time and duration of non-hypoxaemic apnoea with good tolerability.

The main goal of pre-oxygenation is to boost the body's oxygen reserves and thus, increase the safety of induction and tracheal intubation. When the patient is apnoeic, the body's main oxygen reserves are held in the lungs. These reserves cross the gas-blood interface and bind to haemoglobin.18 The lung's oxygen capacity depends on the aerated volume at rest, which is related to the functional residual capacity (FRC). During pre-oxygenation, the air in the lung is replaced by 100% oxygen. However, atelectasis appears soon after induction of anaesthesia because the diaphragm rises and the FRC decreases.19 In the present study, the application of PSV may have raised oxygenation by increasing the FRC and reducing intrapulmonary shunt.11, 19–21 In a study performed in morbidly obese patients,22 the application of PEEP during pre-oxygenation decreased the amount of atelectasis and enhanced oxygenation. These results were also confirmed by Futier et al.,10 who demonstrated a greater end-expiratory lung volume and better oxygenation with PSV using PEEP. By using PSV, the higher exhaled tidal volume may indicate better preservation of FRC. PIP and PEEP may act together to improve alveolar recruitment and reduce alveolar derecruitment.10,22,23 Thus, PSV may have ensured lung homeostasis and increased the oxygen reserves, resulting in a longer duration of non-hypoxaemic apnoea.

We also sought to determine whether PIP associated with PEEP had an effect on oxygen cost of breathing and thus the duration of non-hypoxaemic apnoea. The most frequently reported effect of PIP concerns the distribution of minute ventilation between the respiratory rate and tidal volume. MacIntyre24 demonstrated that for a given minute ventilation, the ventilation rate was inversely related to the PIP. Furthermore, the use of PIP may decrease respiratory work and the oxygen cost of breathing.24,25 In the present study, we did not observe a significant intergroup difference in the ventilation rate whereas tidal volume was higher in the PSV group. As previously explained, high exhaled tidal volume may be related to the effects of PIP and PEEP on alveolar recruitment/derecruitment. In the absence of a non-PIP PSV group, we cannot conclude that PIP has a significant, additive effect on pre-oxygenation.

Our study had a number of limitations. The two groups differed in term of sex ratio and baseline SpO2. As our results remained unchanged after adjustment, we can conclude that the effect of these factors were marginal. We measured the overall duration of the pan-endoscopy and thus did not exclude interruptions. One can suppose that the overall duration of the pan-endoscopy would be shorter if there are no interruptions. Another limitation concerns the detection of apnoea during the examination; the resumption of spontaneous ventilation was only assessed clinically, so it would have been better to measure end-tidal carbon dioxide concentration during the examination. However, this measurement was prevented by the absence of tracheal intubation. The PIP and PEEP parameters were chosen on the basis of the results published by Tanoubi et al.,13 that is the demonstration that a PIP of 4 cmH2O was equivalent to a PIP of 6 cmH2O in terms of the time course and quality of pre-oxygenation but was better tolerated by the patient. Finally, as mentioned above, the absence of a PSV group without PIP prevents us from drawing firm conclusions about the effects of PIP on the duration of non-hypoxaemic apnoea.

In conclusion, the use of PSV to pre-oxygenate patients during pan-endoscopy was associated with a longer duration of non-hypoxaemic apnoea and less frequent need to ventilate the lungs manually compared with the control group. The use of PSV was also associated with a shorter pre-oxygenation time and greater pre-oxygenation success rate. This approach may be of value in patients at risk of poor ventilation. Indeed, PSV could be performed as a first-line treatment prior to general anaesthesia to counter any unforeseen intubation problems.

Acknowledgements relating to this article

Assistance with the study: none.

Financial support and sponsorship: none.

Conflict of interest: none.

Presentation: data from this study were presented at the Congrès National de la Société Française d’Anesthésie-Réanimation in 2014.


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