Free
Clinical Science  |   November 1997
Difficult or Impossible Ventilation after Sufentanil-induced Anesthesia Is Caused Primarily by Vocal Cord Closure 
Author Notes
  • (Bennett, Abrams, Riper) Assistant Professor of Anesthesiology.
  • (Horrow) Professor of Anesthesiology.
  • Received from the Department of Anesthesiology, Hahnemann Division, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania. Submitted for publication February 5, 1997. Accepted for publication May 30, 1997. Presented in part at the 46th annual meeting of the American Society of Anesthesiologists, October 25, 1995, Atlanta, Georgia, and at the 1997 annual meeting of the Association of University Anesthesiologists, Washington, DC.
  • Address reprint requests to Dr. Bennett: Allegheny University of the Health Sciences, Hahnemann Division, Broad and Vine Streets, Philadelphia, Pennsylvania 19102–1192. Address electronic mail to: BennettJ@auhs.edu.
Article Information
Clinical Science
Clinical Science   |   November 1997
Difficult or Impossible Ventilation after Sufentanil-induced Anesthesia Is Caused Primarily by Vocal Cord Closure 
Anesthesiology 11 1997, Vol.87, 1070-1074. doi:
Anesthesiology 11 1997, Vol.87, 1070-1074. doi:
Opioid-based anesthetic techniques are the most commonly used anesthetic regimens for patients undergoing cardiac surgery. These techniques provide unparalleled hemodynamic stability, blunting of the neuroendocrine responses to surgical stimulation, and postoperative analgesia. [1 ] Opioid-based induction techniques are often complicated by muscular rigidity and difficult ventilation. [2 ] This phenomenon was first described by Hamilton and Cullen in 1953. [3 ] The sequelae of difficult ventilation are clinically important and can include hypertension, hypoxemia, pulmonary hypertension, respiratory acidosis, and increased intracranial pressure. [4–6 ] The incidence of this complication varies depending on the opioid and dose used and the rate at which it is administered. The reported incidence of difficult ventilation after a moderate dose of sufentanil ranges from 84–100%. [7,8 ]
The recent release of an ultra-short-acting esterase-metabolized opioid may increase the incidence of difficult ventilation in the general operating room population. [9 ] This heightens the need for a clear understanding of the cause of this phenomenon.
Difficult or impossible ventilation after opioid induction is commonly ascribed to rigidity of the abdominal and thoracic musculature. [10,11 ] There has been some evidence in the literature that a glottic or supraglottic mechanism may be responsible. [12–15 ] This study further elucidates the contribution of the glottis and supraglottic structures to this clinical problem.
Materials and Methods 
Thirty patients provided informed consent to enter this institutional review board-approved study. Patients underwent elective coronary revascularization, valve repair or replacement, or both. Patients were excluded if they were older than 90 yr, had undergone previous thoracic surgery, had significant pulmonary disease, were morbidly obese (as defined by a body weight > 100 kg), or had a history or physical examination suggesting either an airway abnormality or difficulty with intubation.
Morphine sulfate (0.1 mg/kg) and scopolamine (0.006 mg/kg) given intramuscularly provided preoperative sedation and control of airway secretions. All patients received intravenous, arterial, and pulmonary arterial catheters placed with local anesthesia. Midazolam (1–2 mg) given intravenously provided additional sedation as needed. The oral and pharyngeal mucosa were topically anesthetized with 5% lidocaine ointment and 10% lidocaine spray (Astra Pharmaceuticals, Westborough, MA).
A split fiberoptic Berman style airway was placed, followed by an appropriately sized Patil-Syracuse mask (Anesthesia Associates, San Marcos, CA). Patients breathed 100% oxygen through the mask connected to a semiclosed circle breathing system attached to a standard anesthesia machine. An adult-sized fiberoptic bronchoscope (Pentax model FB19H) was placed through the port in the Patil-Syracuse mask and the airway and positioned just above the opening of the glottis. A color video camera system (Dyonics digital camera system; Smith & Nephew, Andover, MA) attached to the fiberscope provided both real-time video images and color photographs as needed. With the patient breathing quietly, the first photograph was taken at end expiration.
Anesthesia was induced with 3 micro gram/kg sufentanil administered as a 2-minute infusion. Phenylephrine or ephedrine were given intravenously as needed to maintain normal hemodynamics. At the conclusion of the sufentanil infusion, a photograph was taken of the glottis, after which the fiber scope was removed and the mask port closed off with the attached cap. The anesthesia machine ventilator provided 10 ml/kg tidal volume breaths at a rate of 10 per min through the mask and airway during a maximal jaw thrust maneuver. A capnograph side stream spirometer (Datex Capnograph Ultima; Helsinki, Finland) placed in the breathing circuit just proximal to the mask provided measurements of dynamic pulmonary compliance (Exhaled volume/plateau pressure-positive end-expiratory pressure). [16 ] Data from five sequential breaths were recorded. The median value was used for analysis. Bag mask ventilation was then attempted and subjectively scored as follows; 0, cannot empty gas from the breathing bag; 1, able to ventilate with greater than normal effort; 2, able to ventilate with usual effort; 3, near-effortless ventilation.
After the data were recorded as just described, 0.1 mg/kg pancuronium given as a bolus provided muscle relaxation. One minute after muscle relaxants were given, subjective and objective compliances were measured again. Then the fiberscope was placed in the airway to obtain a third photograph. The patients were intubated either with the aid of fiberscope or by direct laryngoscopy at the discretion of the attending anesthesiologist.
The photographs obtained for all patients were coded by a research assistant, randomized, and then scored by one of the authors (J.C.H.) not present for any of the inductions. The photographs were scored as 1 = vocal cords opened, 2 = vocal cords partially closed, or 3 = vocal cords closed.
The Wilcoxon signed rank test compared subjective and objective compliance data. Freidman's nonparametric analysis of variance was used for picture score data. A significant effect of time was analyzed further by pairwise Bonferroni-corrected Wilcoxon signed rank tests. The study design allowed the patients to act as their own controls.
Results 
Thirty patients completed the study protocol. Twenty-eight of the thirty patients exhibited severely compromised subjective and objective measures of pulmonary compliance after the induction of anesthesia with sufentanil. All 28 of these patients had closed vocal cords at the time of postopioid photography. Pooled data for all patients showed compromised subjective compliance (median score, 0.0 ml/cm H2O; range, 0–2 ml/cm H2O) and objective compliance (median score, 7.0 ml/cm H2O; range, 1–55 ml/cm H2O) after induction. Both subjective (median score, 3 ml/cm H2O; range, 1–3 ml/cm H2O) and objective compliance (median, 54.ml/cm H2O; range, 27–95 ml/cm H2O) improved after the muscle relaxant was given (P < 0.00002 for each;Table 1). All patients scored 1 or 2 (cords opened) before the opioid was given. The median score after opioid was 3 (cords closed: range, 1–3; P = 0.00002). After relaxant, median score was 1 (cords opened: range, 1–2; P = 0.00005). The two patients who did not exhibit severely compromised compliance values after anesthetic induction had opened vocal cords at the postopioid photograph (picture scores = 1;Table 1).
Table 1. Objective/Subjective Compliance Data and Picture Scores 
Image not available
Table 1. Objective/Subjective Compliance Data and Picture Scores 
×
Many of the patients whose vocal cords closed after the infusion of sufentanil also exhibited an involution of the epiglottis and the aryepiglottic structures (see Figure 1). The involution of the glottic structures is similar to the airway changes of laryngospasm. [17 ]
Figure 1. Photographs obtained from patient 1.
Figure 1. Photographs obtained from patient 1.
Figure 1. Photographs obtained from patient 1.
×
Discussion 
An increase in chest and abdominal wall muscle tone is most frequently cited as the cause of difficult ventilation after opioid induction of anesthesia. [10,11 ] In 1983 Scamman [12 ] noticed that patients with tracheostomies placed under local anesthesia before the induction of general anesthesia with 17 micro gram/kg fentanyl experienced only a small decrement in pulmonary compliance. However, an identical induction sequence in patients with natural airways resulted in impossible ventilation. Arandia and Patil, [13 ] in a letter to the editor, described difficult ventilation in patients after opioid induction. Fiberoptic visualization of the glottis revealed closed vocal cords in some. They also described patients who had opened vocal cords but could not be ventilated. They ascribed this finding to chest wall, abdominal rigidity, or both.
Abrams et al. [14 ] recently reported that preinduction placement of an oral tracheal tube allows a minimal decrement in ventilatory compliance on opioid induction of anesthesia. The current study goes further in demonstrating closure of the glottis and supraglottic structures as the proximate cause of difficult ventilation after a sufentanil infusion. Patients in this study displayed a 93% incidence of difficult ventilation after the 3-micro gram/kg dose of sufentanil, which corresponds with the 84% incidence previously reported using a similar protocol. [6 ]
This protocol did not allow us to determine what contribution, if any, contraction of the chest and abdominal musculature make to the experience of difficult ventilation after sufentanil induction of anesthesia. Data from the study by Abrams et al. [14 ] showed a statistically insignificant change in pulmonary compliance after opioid induction in intubated patients. It is likely that in adults, this mechanism makes a minor contribution to the problem of difficult or impossible ventilation after opioid induction of anesthesia. To obtain accurate measurements of ventilatory compliance using an unintubated airway requires an excellent mask seal, proper placement of an oral airway, and use of an aggressive jaw thrust maneuver. We have used this technique in several studies [6,14 ] and our data are consistent across the different protocols. We are confident that the changes in compliance demonstrated after opioid induction of anesthesia are not caused by airway obstruction above the level of the glottis.
The exact mechanism of increased muscle tone after the rapid infusion of an opioid is not known. Recent animal work indicates that stimulation of central micro1receptors increases efferent motor traffic, resulting in muscle contraction and rigidity. Activation of K sub 1 and Delta1receptors can attenuate this response. [18 ]
Because muscle contraction requires an intact neuromuscular junction, neuromuscular blockade effectively terminates the clinical signs of opioid-induced rigidity. Priming alone with a nondepolarizing muscle relaxant does not effectively prevent rigidity. [6 ] A simultaneous infusion of relaxant and opioid allow smooth induction without compromising ventilatory compliance. [6,19 ] Jaffe and Ramsey [20 ] independently noted that the administration of nondepolarizing muscle relaxants resolved the ventilatory embarrassment caused by opioids before the train-of-four measured at the adductor pollicis was affected. Both nondepolarizing and depolarizing muscle relaxants have been shown effectively to relax the laryngeal musculature before they have any effect on peripheral neuromuscular function. [21,22 ] Understanding that laryngeal closure is the cause of opioid-induced difficult ventilation explains why the administration of muscle relaxants rapidly allows effective ventilation.
Focusing on activation of the laryngeal musculature as the proximate cause of difficult ventilation after opioid administration suggests that the administration of a small dose of a rapidly acting neuromuscular blocking agent may prevent this clinical problem. [23 ] Additional investigations will explore this possibility.
References 
References 
Waller JL, Hug CC, Nagle DM, Craver JM: Hemodynamic changes during fentanyl oxygen anesthesia for aortocoronary bypass operation. Anesthesiology 1981; 55:212-17.
Comstock M, Scamman F, Moyers J, Stevens W: Rigidity and hypercarbia associated with high dose fentanyl induction of anesthesia. Anesth Analg 1981; 60:362-3.
Hamilton W, Cullen S: Effect of levallorphan tartrate upon opiate-induced respiratory depression. Anesthesiology 1953; 14:550-5.
Benthuysen J, Smith N, Sanford T, et al: Physiology of alfentanil-induced rigidity. Anesthesiology 1986; 64:440-46.
Mets B, James MFM: Another complication of opiate-induced chest wall rigidity. S Afr Med J 1992; 81:385-6.
Benthuysen J, Kien N, Quam D, Martucci R. Intracranial pressure increases during alfentanil-induced rigidity. Anesthesiology 1988; 68:438-40.
Horrow JC, Abrams JT, Van Riper DF, Lambson DL, Storella RJ: Ventilatory compliance after three sufentanil-pancuronium induction sequences. Anesthesiology 1991; 75:969-74.
Weinger MB: Opiate induced muscle rigidity clinical implications and pathophysiology. Progress in Anesthesiology, Vol. 8. San Antonio Texas, Dannemiller Memorial Educational foundation, 1993, pp 198-210.
Burkle H, Dunbar S, Van Aken H: Remifentanil: a novel, short-acting, mu opioid. Anesth Analg 1996; 83:646-51.
Bailey PL, Stanley TH: Intravenous opioid anesthetics, Anesthesia, Fourth edition. Edited by Miller RD, et al., New York, Churchill Livingstone, 1994, pp 291-323.
Coda BS: Opioids, Clinical Anesthesia, third Edition. Edited by Barash PG, Cullen BF, Stoelting RK. Philadelphia, Lippincott-Raven, 1996, pp 329-58.
Scamman FL: Fentanyl-0 sub 2-N sub 2 O rigidity and pulmonary compliance. Anesth Analg 1983; 62:332-34.
Arandia HY, Patil VU: Glottic closure following large doses of fentanyl [Letter]. Anesthesiology 1987; 66:574-5.
Abrams JT, Horrow JC, Bennett JA, Van Riper DF, Storella RJ: Upper airway closure: a primary source of difficult ventilation with sufentanil induction of Anesthesia. Anesth Analg 1996; 83:629-32.
Bennett JA, Abrams JT, Van Riper D, Horrow JC: Difficult ventilation after opioid induction is caused by laryngospasm [Abstract]. Anesthesiology 1995; 83:S74.
Merilainen P, Hanninen H, Tuomaala L: A novel sensor for routine continuous spirometry of intubated patients. J Clin Monitor 1993; 9:374-80.
Fink RB, Demarest RJ: Laryngeal biomechanics. Cambridge, MA, Harvard University Press, 1978, pp 45-64.
Vancova ME, Weinger MB, Chen DY, Bronson JB, Motis V, Koob GF: Role of central Mu, delta-1 and kappa-1 opioid receptors in opioid-induced muscle rigidity in the rat. Anesthesiology 1996; 85:574-83.
Hill AB, Nahrwold ML, Rosayro AM, Knight PR, Jones RM, Bolles RE: Prevention of rigidity during fentanyl-oxygen induction of anesthesia. Anesthesiology 1981; 55:452-4.
Jaffe TB, Ramsey FM: Attenuation of fentanyl-induced truncal rigidity. Anesthesiology 1983; 58:562-4.
Donati F, Meistelman C, Plaud B: Vecuronium neuromuscular blockade at the adductor muscles of the larynx and adductor pollicis. Anesthesiology 1991; 74:833-7.
Meistelman C, Plaud B, Donati F: Neuromuscular effects of succinylcholine on the vocal cords and adductor pollicis muscles. Anesth Analg 1991; 73:278-82.
Chung DC, Rowbottom SJ: A very small dose of suxamethonium relieves laryngospasm. Anesthesia 1993; 43:229-30.
Figure 1. Photographs obtained from patient 1.
Figure 1. Photographs obtained from patient 1.
Figure 1. Photographs obtained from patient 1.
×
Table 1. Objective/Subjective Compliance Data and Picture Scores 
Image not available
Table 1. Objective/Subjective Compliance Data and Picture Scores 
×