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Anesth Analg 1999;89:762
© 1999 International Anesthesia Research Society

GENERAL ARTICLES

Postoperative Obstructive Apnea

G. Dhonneur, MD, X. Combes, MD, B. Leroux, MD, and P. Duvaldestin, MD

Department of Anesthesia, University of Paris, Val de Marne, Hopital Henri Mondor, Créteil, France

Address correspondence and reprint requests to G. Dhonneur, Service d'Anesthésie et Réanimation Chirurgicale, Hopital Henri Mondor, 94010 Créteil, France. Address e-mail to gillesdhonneur{at}hmn .ap-hop-paris.fr.


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
We studied electromyography (EMG) of the geniohyoid muscle (Gh) and diaphragm (Di) in 12 postoperative, premedicated (flunitrazepam 2 mg PO), asymptomatic patients who snored after recovering from general anesthesia, the induction of which was partly achieved by IV midazolam. After extubation of the trachea, integrated EMG activity of Gh (E-GhMTA) and Di (E-DiMTA) were measured. For Gh, tonic and phasic activity were distinguished. Patients were studied during obstructive apnea, at the end of apnea, while breathing through an artificial Guedel airway, and during quiet breathing 5 min after flumazemil. All patients experienced episodes of postoperative upper airway obstruction and nine became apneic. Flumazenil restored consciousness and predominant tonic E-GhMTA associated with upper airway patency in all patients. Reduced tonic E-GhMTA characterized postoperative obstructive apnea. Resolution of apnea required a burst of both tonic and phasic E-GhMTA associated with intense E-DiMTA. Breathing through the Guedal airway resulted in patent airway in 8 of 10 patients and was associated with low tonic and phasic E-GhMTA and reduced E-DiMTA. In this study, we demonstrated that the tonic pharyngeal muscular support modulates airway patency in the postoperative period. Because it is reversed by flumazemil, benzodiazepines are certainly the main cause of airway obstruction in these patients.

Implications: Upper airway obstruction during recovery from general anesthesia induced by IV midazolam is associated with low tonic pharyngeal muscular support, which modulates upper airway patency in the postoperative period.


   Introduction
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 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
In the postoperative period, the residual depressant effects of anesthetics on neural control of respiration seems crucial resulting in upper airway obstruction, which is one of the principle mechanisms contributing to hypoxemia during this period (1). In common with sleep apnea syndrome, we hypothetized that postoperative obstructive apneas may be caused by a decrease in neural drive (2,3), selective inhibition (4) of the muscles contributing to dilation of the collapsible part of the upper airway and that of the diaphragm (5). We investigated the residual effects of benzodiazepine on muscles contributing to upper airway patency. We measured the electromyographic (EMG) activity of the geniohyoid muscle and the diaphragm during recovery from midazolam-induced anesthesia in a population of snoring patients prone to sleep-induced upper airway collapsibility. We designed the study to assess the changes occurring in the EMG of contraction of both inspiratory muscles during defined periods: obstructive apnea, while breathing through a Guedel cannula, and after the administration of the benzodiazepine antagonist flumazenil.


   Methods
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 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
This study was approved by our hospital ethics committee on human research, and informed, written consent was obtained from each patient. Twelve male ASA physical status I or II patients, not taking sleeping medication, without predictable difficult airway or craniofacial dysmorphism were assessed preoperatively before entry into the study. Selected patients without history of cardiorespiratory disease were classified as simple snorers on bed partner sleep observation and Epworth Sleepness Score (6) (8.2 ± 1.8; mean ± SEM). Each patient was scheduled to undergo elective, short-duration orthopedic surgery on the lower limbs under general anesthesia.

Premedication consisted of flunitrazepam 2 mg given orally 1 h before the induction of anesthesia. Anesthesia was induced with midazolam 0.25 mg/kg, alfentanil 20 µg/kg, and vecuronium 0.1 mg/kg to facilitate tracheal intubation. Anesthesia was maintained using nitrous oxide 60% in oxygen and isoflurane 0.7%–2.0% as required. Controlled ventilation was adjusted to maintain the end-tidal CO2 concentration at 4.5% ± 0.2%. Neuromuscular function was monitored by ulnar nerve stimulation in train-of-four mode. For the purpose of the study, the patients were transported to the recovery room before recovery from anesthesia.

When four evoked thumb twitches were observed, neostigmine 40 µg/kg and atropine 20 µg/kg were administered IV. Once patients were arousable to verbal stimuli and had fully recovered from neuromuscular blockade, tracheal extubation was performed.

Throughout the study, the patients breathed an oxygen/air mixture delivered under a hood canopy (fraction of inspired oxygen 0.35–0.50), a flow of 30 L/min through the canopy being maintained to eliminate rebreathing. Pulse oximetry (SpO2) was continuously monitored. At 20–35 min postextubation, patients were given a 0.5-mg IV flumazenil bolus, followed by a continuous infusion of 0.5 mg over the next 30 min.

All patients were studied in the supine position after tracheal extubation for 10 min after flumazenil administration. To limit displacement of the hyo-eppiglotic structures, the head and cervical spine were maintained in a neutral position using a deflated pediatric vacuum mattress placed under the shoulders and ascending to the top of the skull.

In the recovery room, EMG activity of the geniohyoid and the diaphragm was measured simultaneously using percutaneous Teflon-insulated wire electrodes (0.1-mm diameter) (Xomed, Jacksonville, FL) placed approximately 1 cm apart, which were inserted intramuscularly while the patients were still anesthetized. EMG activity of the geniohyoid muscle was measured by using the method described by Wiegang et al. (7). Two sterile 22-gauge needles containing the wires were inserted percutaneously 1.5–2.5 cm into the skin surface midway between the mentum and the hyoid bone 1 cm laterally to the submental midline. Diaphragmatic activity was recorded by using the method of Bolton et al. (8). After an intercostal nerve blockade was performed using 9 mL of 2% lidocaine in the same and the immediately adjacent (inf and sup) interspace (sup and 5 cm posteriorly to the electrodes to prevent inspiratory intercostal muscle activity), the wires were inserted in the right seventh or eighth interspace between anterior axillary and midclavicular lines. The EMG signals were amplified, pass band-filtered (low-frequency time constant 0.03 s, high-frequency cutoff 3 KHz), and electronically integrated on a "moving time-averaged" basis with a time constant of 100 ms.

Nasal or buccal airflow was assessed by using a thermistor probe (Nihon Kohden, Claye-Souilly, France).

The Ramsey sedation (9) score composed of five items (0 = comatose, 1 = responsive to noxious stimuli, 2 = arousable on calling, 3 = awake, 4 = tense) was measured throughout the study.

All signals were continuously registered on a paper recorder. The integrated EMG and respiratory pattern signals were recorded with MAC LAB 8 recorder/logger system (Materiel AD. Instruments, Phymep, Paris, France).

Obstructive apnea was defined as an episode of cessation of airflow of >10-s duration, whereas inspiratory effort, as determined by electromyographic activity of the diaphragm (E-DiMTA) tracing, was associated with paradoxical abdominal and ribcage motions. Timing of all respiratory cycles (Fig. 1) was based on diaphragmatic EMG activity (integral of the E-DiMTA signal). Electrical inspiration was defined as the time from onset to offset of E-DiMTA.



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  		Figure 1. Representative tracing of raw and integrated (time constant 100 ms) electromyographic (EMG) activity versus time of the geniohyoid muscle (E-Gh, E-GhMTA) and of the diaphragm (E-Di, E-DiMTA). EGhMTA is expressed as the percentage of maximal activity. Timing of all respiratory cycles is based on diaphragmatic EMG activity. Electrical inspiration is defined as the time elapsing onset to offset E-DiMTA (Ti). Two different modes of E-GhMTA muscular activity are distinguished: tonic end-expiratory activity and phasic inspiratory activity, defined as total peak activity minus tonic activity.

 
The gain was adjusted for both studied muscles to provide sufficient deflections, then remained unchanged for the remainder of the study. Consequently, EMG measurements of both muscles in each patient had their own arbitrary units. Two different modes of geniohyoid muscular activity were distinguished as defined by Wiegand et al. (7): tonic expiratory activity (tonic), which is the activity recorded just before onset of electrical inspiration; and phasic inspiratory activity (phasic), defined as total peak inspiratory electromyographic activity of the geniohyoid (E-GhMTA) minus tonic activity (Fig. 1). At the end of the procedure, the electrode wires were shorted with an electrocardiogram (ECG) electrode on the skin of the patient, and the resultant signal was recorded to provide a baseline for the integrated EMG signals. The amplitude of tonic and phasic E-GhMTA and E-DiMTA are expressed using a linear scale of arbitrary units graded from 0% to 100%, where 0 is the baseline value and 100% is the maximal level of recorded EMG activity for each patient during the study.

The mean tonic and phasic E-GhMTA and mean E-DiMTA activity was measured from at least three breaths during four stages: obstructive apnea episode (APN); at apnea resolution (RES), corresponding to the last obstructed breaths leading to ventilation resumption; while breathing through an artificial Guedel airway (GAW) with persistent signs of obstructive apnea; and during quiet breathing 5 min after flumazenil administration (FLU).

Data are expressed as mean ± SEM. Statistical analysis was performed by using the Friedman two-way analysis of variance. P < 0.05 was considered significant.


   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Duration of anesthesia, defined as the time from tracheal intubation to extubation, was 58 ± 12 min (Table 1). Patients were studied 22 ± 8 min after their admission to the recovery room. Postoperative sleep characteristics are presented in Table 2. All patients demonstrated cyclical periods of obstructive respiratory events, and nine patients experienced obstructive apnea followed by transient episodes of resolution of apnea, as seen in a representative tracing from one patient (Fig. 2). No patient showed serious arterial oxygen desaturation (SpO2 < 91%). Forty-three episodes of apnea were analyzed and 728 cycles were measured.


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  		Table 1. Details of Patients
 

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  		Table 2. Preoperative Sleep Characteristicsa
 


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  		Figure 2. Representative tracing from one patient during recovery from midazolam-induced general anesthesia, showing electromyographic activity of geniohyoid (E-Gh, E-GhMTA) and diaphragm (E-Di, E-DiMTA), nasobuccal thermistor airflow (NBA), and ribcage (RC) and abdominal (AB) motions.

 
Mean muscle EMG activities observed during the four time periods studied are presented in Table 3 and Figure 3. During APN, peak E-GhMTA increased progressively. Airflow resumption was associated with a sudden burst in phasic and tonic E-GhMTA and increased E-DiMTA. Maximal geniohyoid and diaphragmatic EMG peak activities were invariably observed in ventilatory cycles immediately preceding apnea resolution. Phasic E-GhMTA increased (P < 0.01) from 39% ± 19% during APN to 82% ± 16% during RES. Tonic E-GhMTA activity significantly increased (P < 0.01) from 19% ± 8% of maximal activity during APN to 85% ± 12% at RES.


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  		Table 3. Integrated Electromyographic Activity of the Geniohyoid Muscle (E-GhMTA) and the Diaphragm (E-DiMTA) During Recovery from Anesthesia
 


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  		Figure 3. E-GhMTA activities (phasic and tonic) and E-GhMTA at the four time periods of the study: during apnea (APN), resumption of apnea (RES), insertion of the Guedel airway (GAW), and after flumazemil administration (FLU). °P < 0.01 versus APN. *P < 0.05 versus GAW.

 
In two patients, the insertion of the Guedel cannula was not possible because of gag reflex and arousal. In two patients, some degree of airway obstruction with noisy breathing and sustained phasic E-GhMTA breathing persisted despite Guedel cannula insertion. In 8 of 12 patients, breathing through the Guedel cannula restored complete airway patency. In the 10 patients who used the Guedel cannula, tonic and phasic modes of the geniohyoid muscle and phasic mode of the diaphragm were 8% ± 6%, 13% ± 8%, and 24% ± 12% of their maximal activity, respectively.

Complete arousal was observed in all patients within 3 min after the initial bolus flumazemil administration (sedation score 3.2 ± 0.2). Five minutes after the flumazemil bolus injection, phasic E-GhMTA was 13% ± 8% of maximal activity. Tonic E-GhMTA was 49% ± 10% of maximal activity, significantly (P < 0.05) higher than during GAW.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
We demonstrated that postoperative obstructive apneic episodes occurring in snoring patients in whom anesthesia was partly achieved with midazolam are characterized by a dramatic decrease in the tonic activity of glossal muscles, whereas the phasic activity synchronous to inspiratory efforts is increased. RES was preceded by a burst in both tonic and phasic Gh activity and diaphragmatic activity. Flumazemil administration restored the normal breathing pattern associated with a high level of tonic and extinguishment of phasic glossal muscular support.

We studied the geniohyoid muscle because of its predictable anatomic location and phasic inspiratory activity (7). It was, however, not feasible to confirm electrode position within the geniohyoid muscle during EMG recording. Therefore, the possibility that our EMG recording reflects activity of the overlying genioglossus cannot be eliminated, so that our observations can be viewed as an assessment of pharyngeal dilatators muscular activity during the postoperative period. Because EMG activity was not measured preoperatively, we cannot use baseline reference values corresponding to breathing patterns and EMG activity in the unanesthetized state. We assume that normal breathing conditions were met after IV flumazenil administration because complete arousal associated with normal breathing pattern was then observed.

In the conditions of our study, residual effects of other anesthetics coadministrated with benzodiazepines might have favored airway obstruction. Because of clinical neuromuscular block monitoring and reversal, partial paralysis is probably not implicated in postoperative obstructive respiratory disturbance (10). However, the residual effects of potent centrally acting narcotic analgesics probably amplified the benzodiazepine-induced glossal muscular effects (11). However, the full recovery of consciousness observed five minutes after flumazemil administration suggests that benzodiazepines may have been the major cause of upper airway obstruction in our patients. Therefore, midazolam appears as the principal drug, although residual effects of flunitrazepam may have also contributed to postoperative airway obstruction through its long elimination half-life (12).

The results of our EMG measurements demonstrated that, during postoperative obstructive apneas, the tonic mode of activity of the geniohyoid muscle was dramatically reduced, but its phasic component was increased. Similar observations were described by Drummond (13,14). It was demonstrated in experimental settings that tonic and phasic upper airway muscle activity is controlled by two subsets of respiratory neurons whose sensitivity to depressants differs. Motor units of upper airway muscles contributing to tonic activity were depressed during sleep, whereas those contributing to the phasic activity, which receive a greater efferent input from medullary neurons, were preserved (15). We assume that benzodiazepine-induced sedation mainly depresses the tonic component of geniohyoid muscle activity, making the pharynx more sensitive to dynamic collapse. Comparisons of pharyngeal muscular activity modes between unobstructed breathing in the nonreversed state (GAW) and quiet breathing in the reversed state (FLU) suggest that benzodiazepines reversal increases tonic muscle activity in the geniohyoid, which prevents apnea.

As shown in sleep studies, we observed a progressive increase in EMG activity in both the diaphragm and the tonic and phasic activities of the geniohyoid muscle during periods of obstructive apnea (16,17). During apnea, stimuli may be involved in upper airway reopening, including chemical (16,18) or mechanical (19) triggers arising during prolonged inspiratory efforts against an occluded airway. In the present study, supplemental oxygen promoted high SpO2 levels, but hypercarbia developing during obstructive apnea may have enhanced chemoreceptor activity and central respiratory drive. Moreover, airway reopening required not only an intense diaphragmatic activity, but also a burst in tonic geniohyoid activity. Our observations are consistent with the assertion that such intense tonic response could be part of a protective reflex originating from upper airway mechanoreceptors (20).

The changes in geniohyoid muscle and diaphragmatic activity induced by the insertion of the Guedel cannula reinforce the hypothesis that the phasic activity of upper airway dilators responds predominantly to mechanoreceptors, rather than to chemical stimuli (21). Indeed, we observed that the breathing pattern induced by the Guedel cannula was concomitant with an abrupt decrease in both phasic geniohyoid and diaphragmatic activity. Chemoreceptor activation would have suggested a lag time between airway manipulation and pharyngeal dilators or diaphragm response.

In conclusion, in this study, we demonstrated that the tonic pharyngeal muscular support modulates airway patency in the postoperative period. We observed that benzodiazepine-induced general anesthesia may be associated with low tonic pharyngeal muscular support, resulting in postoperative upper airway obstruction. Resumption of obstructive apnea is preceded by increased tonic and phasic activity of the upper airway muscles and of the diaphragm. Flumazenil administration restored tonic pharyngeal muscular support and a normal breathing pattern in each patient. From the present results, we believe that the administration of a benzodiazepine to induce general anesthesia in patients with a history of snoring, which is a rather common finding in the normal population, may increase the incidence of postoperative obstructive and hypoxemic respiratory events.


   Acknowledgments
 
This work was supported by l'Association pour la Promotion de la Recherche Clinique de l'APHP.


   Footnotes
 
This work was presented in part at the 37th annual meeting of the French Society of Anesthesiology, September 1996.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Hoffstein V, Zamel N. Sleep apnea and the upper airway. Br J Anaesth 1990;65:139–50.[Free Full Text]
  2. Nishino T, Shirahata M, Yonezawa T, Honda Y. Comparison of changes in the hypoglossal and the phrenic nerve activity in response to increasing depth of anesthesia in cats. Anesthesiology 1984;60:19–24.[ISI][Medline]
  3. Hwang J, John WM, Bartlett D. Respiratory-related hypoglossal nerve activity influences of anesthetics. J Appl Physiol 1983;78:785–92.
  4. Ochiai R, Guthrie RD, Motoyama E. Effects of varying concentrations of halothane on the activity of the genioglossus, intercostals and diaphragm in cats an electromyographic study. Anesthesiology 1989;70:812–6.[ISI][Medline]
  5. Hudgel D, Harasick T. Fluctuation in timing of upper airway and chest wall inspiratory activity in obstructive sleep apnea. J Appl Physiol 1990;69:443–50.[Abstract/Free Full Text]
  6. Gentil B, Lienhart A, Fleury B. Enhancement of postoperative desaturation in heavy snorers. Anesth Analg 1995;81:389–93.[Abstract]
  7. Wiegand D, Latz B, Zwillich CW, Wiegand L. Geniohyoid muscle activity in normal men during wakefulness and sleep. J Appl Physiol 1990;69:1262–9.[Abstract/Free Full Text]
  8. Bolton CF, Grand'Maison F, Parkes A, Shkrum M. Needle electromyography of the diaphragm. Muscle Nerve 1992;15:678–81.[ISI][Medline]
  9. Ramsay MAE, Savage TM, Simpson BRJ, Goodwin R. Controlled sedation with alfaxolone-alphadolone. Br Med J 1974;2:656–9.
  10. Pavlin EG, Holle RH, Schoene RB. Recovery of airway protection compared with ventilation in humans after paralysis with curare. Anesthesiology 1989;70:381–5.[ISI][Medline]
  11. Ghouri AF, Bodner M, White PF. Recovery profile after desflurane-nitrous oxide versus isoflurane-nitrous oxide in out patients. Anesthesiology 1991;74:419–24.[ISI][Medline]
  12. Cano JP, Soliva M, Hartmann D, et al. Bioavailability of various galenic formulations of flunitrazepam. Drug Res 1977;27:2383–8.[Medline]
  13. Drummond GB. Influence of thiopentone on upper airway muscles. Br J Anaesth 1989;63:12–21.[Abstract/Free Full Text]
  14. Drummond GB. Comparison of sedation with midazolam and ketamine effects on upper airway muscle activity. Br J Anaesth 1996;76:663–7.[Abstract/Free Full Text]
  15. Orem J, Osorio I, Brooks E, Dick T. Activity of respiratory neurons during NREM sleep. J Neurophysiol 1985;54:1144–56.[Abstract/Free Full Text]
  16. Remmers JE, DeGroot WJ, Sauerland EK, Anch AM. Pathogenesis of upper airway occlusion during sleep. J Appl Physiol 1978;44:931–8.[Free Full Text]
  17. Hudgel D, Chapnam KR, Faulks C, Hendricks C. Changes in inspiratory muscle electrical activity and upper airway resistance during periodic breathing induced by hypoxia during sleep. Rev Respir Dis 1987;135:899–906.
  18. Sillivan CE, Issa FG. Pathophysiologic mechanisms in obstructive sleep apnea. Sleep 1980;3:235–46.[ISI][Medline]
  19. Bowes G, Phillipson EA. Arousal responses to respiratory stimuli during sleep. In: Saunders NC, Sullivan CE, eds. Sleep and breathing. New York:Marcel Dekker, 1984:137–61.
  20. Kimoff RJ, Cheong T, Olha A, et al. Mechanism of apnea termination in obstructive sleep apnea. Med 1994;149:707–14.
  21. Mathew OP, Abu-Osba YK, Tach BT. Influence of upper airway pressure changes on genioglossus muscle respiratory activity. J Appl Physiol 1982;52:438–44.[Abstract/Free Full Text]
Accepted for publication May 14, 1999.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press