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Anesth Analg 2006;102:306-312
© 2006 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000181290.37527.CE

GENERAL ARTICLES

Does the Timing of Tracheal Intubation Based on Neuromuscular Monitoring Decrease Laryngeal Injury? A Randomized, Prospective, Controlled Trial

Thomas Mencke, MD*, Matthias Echternach, MD{dagger}, Peter K. Plinkert, MD{dagger}, Ulrich Johann, MD{ddagger}, Nazan Afan, MD{ddagger}, Hauke Rensing, MD{ddagger}, Gabriele Noeldge-Schomburg, MD*, Heike Knoll, MD{ddagger}, and Reinhard Larsen, MD{ddagger}

*Department of Anaesthesia and Intensive Care Medicine, University of Rostock, Rostock, Germany; {dagger}Department of Otorhinolaryngology, {ddagger}Department of Anaesthesia and Intensive Care Medicine, University of the Saarland, Homburg/Saar, Germany

Address correspondence and reprint requests to Thomas Mencke, MD, Department of Anesthesia and Intensive Care Medicine, University of Rostock, Schillingallee 35, 18057 Rostock, Germany. Address e-mail to thomas.mencke{at}uni-rostock.de.


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Appendix: Assessment of...
 References
 
Vocal cord injuries (VCI) and postoperative hoarseness (PH) are common complications after general anesthesia. Poor muscle relaxation at the moment of tracheal intubation may result in VCI. There is a large interindividual variation in neuromuscular depression after administration of neuromuscular blocking drugs. Therefore, the optimal individual timing of tracheal intubation based on neuromuscular monitoring (monitoring) may decrease VCI. In this prospective trial, 60 patients were randomized into 2 groups: Monitoring group: tracheal intubation at maximum block based on monitoring after atracurium 0.5 mg/kg and 2-min group: tracheal intubation 2 min after injection of atracurium 0.5 mg/kg. Intubating conditions were evaluated with the Copenhagen score. VCI were examined by stroboscopy before and 24 and 72 h after surgery. PH was assessed at 24, 48, and 72 h after surgery by a standardized interview. Excellent intubating conditions were significantly increased in the monitoring group compared with the 2-min group: 8 versus 2 patients, respectively (P = 0.036). The incidence of PH between the study groups was comparable: 7 (monitoring) versus 8 patients (2-min) (P = 0.860). Similar findings were observed for VCI: 9 versus 5 patients; respectively (P = 0.268); type of VCI: thickening of the vocal cords: 8 (monitoring) versus 5 (2-min) patients (P = 0.423), hematomas: 2 patients in each group (not significant). The present study demonstrated that neuromuscular monitoring improved endotracheal intubating conditions. However, tracheal intubation at maximum intensity of neuromuscular block was not associated with a decrease in vocal cord injuries.


   Introduction
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 Abstract
 Introduction
Methods
 Results
 Discussion
 Appendix: Assessment of...
 References
 
Postoperative hoarseness (PH) and sore throat (ST) are common complications after general anesthesia (1–8). PH is the result of at least some degree of laryngeal injury (9). Several risk factors for PH and vocal cord injuries (VCI) have been identified, such as technical and demographic factors, and duration of surgery (2,3,9–13). We demonstrated that tracheal intubating conditions influenced the incidence and severity of laryngeal morbidity, with excellent intubating conditions producing less frequent PH and VCI compared with good or poor conditions (7). Our data indicated that adding neuromuscular blocking drugs (NMBD) to the sequence of induction was associated with better intubating conditions and less PH and VCI (7). However, the large interindividual variation in neuromuscular depression with varying onset times resulted in poor muscle relaxation at the time of intubation, even when NMBDs were used (14–16). The influence of neuromuscular monitoring (monitoring) during induction of anesthesia on laryngeal morbidity, especially VCI, has not yet been investigated in a prospective study.

We sought to assess the incidence and severity of VCI, PH, and ST in patients with tracheal intubation at maximum block determined by monitoring (monitoring group). These data were compared with tracheal intubation 2 min after injection of atracurium 0.5 mg/kg (2-min group).


   Methods
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 Abstract
 Introduction
 Methods
Results
 Discussion
 Appendix: Assessment of...
 References
 
After obtaining approval from the Institutional Review Committee and written informed patient consent, we studied 60 adult patients aged 18–70 yr ASA physical status I or II. All patients underwent orotracheal intubation for elective surgery of the ear. All patients were examined by video-laryngostroboscopy the day before surgery and were not included when preexisting pathologic findings of the larynx were found. Study exclusion criteria were: obesity (defined as weight of 20% or more than the normal weight), pregnancy, preexisting hoarseness or ST, known difficult tracheal intubation and patients suspected to have a difficult airway, i.e., Mallampati airway class score 3 or 4, and mouth opening <3.5 cm. Patients with a difficult intubation, i.e., Cormack and Lehane (17) score of 3 or 4 were excluded after induction of anesthesia.

Patients were randomized into 2 groups of 30 patients each, via random number draws, as follows: 2-min group and monitoring group. After patient arrival in the operating room, standard monitoring was used. Induction of anesthesia was standardized for both groups as follows: at time 0, fentanyl 2 µg/kg was injected and 4 min later, anesthesia was induced with propofol 2.5–3 mg/kg. Anesthesia was maintained with remifentanil 0.20–0.25 µg · kg–1 · min–1 and propofol 4–6 mg · kg–1 · h–1. Ventilation was controlled with oxygen (100%) via a facemask. Ten min later atracurium 0.5 mg/kg (2 x ED95) was injected over a period of 5 s. Tracheal intubation started exactly 2 min later (2-min group) or at maximum T1 depression (monitoring group). Vital signs, i.e., heart rate (HR), and mean arterial blood pressure (MAP), were recorded 30 s after the propofol administration and before tracheal intubation (postinduction values) and 2 min after tracheal intubation (postintubation values). Patients were carefully positioned for surgery and the head was fixed. At the end of surgery, the tracheas were extubated and the patients moved to the postanesthesia care unit (PACU).

In the monitoring group neuromuscular transmission was assessed by electromyography (relaxograph; Datex Instrumentarium Corporation, Helsinki, Finland) on the left hypothenar muscle as described previously (18,19). Measurements started after induction of anesthesia. The relaxograph was set to deliver supramaximal train-of-four stimuli. The first of the four responses was considered the twitch height (T1). After a 10-min period of stabilization and variation of the electromyographic response of <2% for at least 3 min, the relaxograph was recalibrated and control T1 was determined. The following neuromuscular variables were measured: onset time = time between the beginning of injection of atracurium and maximum twitch depression; maximum block = maximum T1 depression (18,19).

Tracheal intubation was performed by the same experienced anesthesiologist who was unaware of the muscular blockade. The intubating score was evaluated on the basis of the consensus conference on Good Clinical Research Practice in Pharmacodynamic Studies of Neuromuscular Blocking Agents (Table 1) (18). In addition, the number of intubation attempts (n) and time of intubation (s), defined as the time from the initial inserting of the laryngoscope until removing the blade from the patient's mouth after successful intubation, were recorded. The following factors were standardized: tube size (men: inner diameter = 8.0 mm, women: inner diameter = 7.0 mm), type of tube (Magill, Lo-ContourTM Murphy Tracheal Tube; Mallinckrodt, Athlone, Ireland), use of a stylet (limited to the tracheal tube), use of lidocaine gel, and intracuff pressure <30 mm Hg.


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  		Table 1. Scoring Conditions for Tracheal Intubation

 

VCI were assessed by video-laryngostroboscopy by an experienced ear-nose-throat physician who was unaware of the patient's group assignment. Stroboscopy uses a synchronized, flashing light passed through a rigid telescope to visualize vocal fold vibration. The flashes of light from the stroboscope are synchronized to the vocal fold vibration at a slightly slower speed, allowing the examiner to observe vocal fold vibration during sound production (20). All patients were examined by stroboscopy at least 3 times: before surgery (and not included when pathologic findings were found) and 24 h and 72 h after surgery. VCI were assessed as follows (7,9,21): location: unilateral (left or right vocal cord) or bilateral (both vocal cords); type of injury: thickening of the vocal folds, hematoma, edema, granuloma. PH was defined as an acoustic quality that was different than the previous voice quality of the patient (20). ST was defined as a continuous throat pain (2). An investigator blinded to patient group assignment asked the patients specific questions in the PACU and on days 1, 2, and 3 after surgery (1,10) (see Appendix). A daily follow-up examination was performed until complete resolution.

Statistical analysis was performed using the SigmaStat® for Windows 2.0 statistical software (SigmaStat, Erkrath, Germany). The required number of patients for the study groups was calculated on the assumption that 43% of the patients had excellent intubating conditions after administration of atracurium 0.5 mg/kg (7) and 85% at maximum blockade as reported by Lieutaud et al. (22). For an 80% power and an {alpha} = 0.05, 53 patients (27 patients in each group) were needed. To compensate for possible dropouts, we enrolled 60 patients, i.e., 30 patients for each group. Results were considered statistically significant when P < 0.05. Data are expressed as mean ± sd or median (range). Demographic data and duration of surgery were analyzed using {chi}2test or Fisher's exact test, and Student's t-test or Mann-Whitney U-test. Analysis of variance on ranks was performed for HR and MAP followed by the Dunnett's post test for multiple comparisons if the analysis of variance on ranks showed significance.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Appendix: Assessment of...
 References
 
Sixty patients were enrolled in this study: 30 patients in each group. Of these 60 patients, 8 (3 patients from the 2-min group and 5 from the monitoring group) were excluded from analysis because of a Cormack grade of 3. Thus, intubating conditions and incidence and severity of VCI, PH, and ST were investigated in the remaining 52 patients: 27 in the 2-min group and 25 in the monitoring group. There were no significant differences between the two groups with respect to demographic data and duration of anesthesia (Table 2).


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  		Table 2. Demographic Data and Duration of Surgery and Anesthesia

 

In both groups, MAP significantly decreased after induction of anesthesia (P < 0.05) and returned to the baseline values after tracheal intubation only in the 2-min group (Table 3).


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  		Table 3. Induction of Anesthesia and Hemodynamic Response to Tracheal Intubation

 

The maximum T1 depression was 94% (range 30%–100%) (Table 4). The onset time in the monitoring group (240 s; range, 120–320 s) was significantly longer than the waiting time of the 2-min group (120 s) (P < 0.001).


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  		Table 4. Neuromuscular Measurements, Intubating Variables, and Intubating Conditions

 

Tracheal intubation was successful in all patients of both groups. Time for intubation, number of attempts, and Cormack grades did not differ significantly between the study groups. The rate of excellent intubating conditions was significantly more frequent in the monitoring group compared with the 2-min group (P = 0.036) (Table 4). Results concerning vocal cord position or movement and reaction to tube insertion or cuff inflation are summarized in Figure 1.



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  		Figure 1. Intubating conditions according the subcomponents vocal cords and reaction to tube insertion or cuff inflation. 2-Min group = Tracheal intubation 2 min after administration of atracurium; monitoring group = Tracheal intubation at maximum block.

 

Stroboscopic examination was performed in all patients at 24 and 72 h after surgery (Table 5). The overall incidence (2-min and monitoring groups together) of VCI was 27% (14 patients). The incidence of VCI did not differ significantly between the monitoring and 2-min groups: 9 versus 5 patients, respectively (P = 0.268). The majority of the VCI was bilateral (12 patients); 2 patients had unilateral (left) VCI. Laryngostroboscopy showed thickening of the vocal folds in 13 patients: 8 monitoring versus 5 2-min patients (P = 0.423). Besides thickening of the vocal folds, 4 hematomas at the vocal cords (2 in each group; not significant) were observed (Fig. 2). Edema and granuloma were not noticed.


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  		Table 5. Incidence of Postoperative Hoarseness, Sore Throat, and Vocal Cord Injuries

 


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  		Figure 2. Thickening of the left vocal fold (localized swelling of the mucosa) at 24 h after surgery (left; arrow) and hematoma (caused by bleeding into a vocal cord) of the left vocal cord at 24 h after surgery (right; arrow).

 

The overall incidence (2-min and monitoring groups together) of PH was 29% (15 patients). The incidence and severity of PH did not differ significantly between groups (Table 5). Overall, 23 patients (44%) suffered from VCI or PH. There was no significant difference between the monitoring and 2-min groups: 11 versus 12 patients, respectively (P = 0.805). No patient suffered from PH or had VCI longer than 3 days. The incidence and severity of ST did not differ significantly between groups (Table 5). There was no correlation between the incidence and severity of PH or VCI and the intubating conditions or subcomponents.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Appendix: Assessment of...
 References
 
The present study demonstrated that excellent intubating conditions were significantly increased after administration of atracurium 0.5 mg/kg in the monitoring group with optimal timing of tracheal intubation based on monitoring compared with the 2-min group with a fixed waiting time of 2-min after administration of atracurium. However, monitoring during induction of anesthesia did not decrease laryngeal injuries, PH, or ST. Moreover, poor intubating conditions in both groups were not associated with an increased laryngeal morbidity.

It was speculated that poor muscle relaxation at the moment of tracheal intubation might have caused many of the observed laryngeal injuries (21,23). We confirmed this assumption: we demonstrated that adding of a NMBD, i.e., atracurium, to the sequence of induction was associated with better intubating conditions and less PH and VCI (7). In our previous study, laryngeal injuries were found in 8% of patients with the use of atracurium and this was significantly decreased compared with the saline group, i.e., without NMBD, with an incidence of 42% (7). However, the large interindividual variation in neuromuscular depression with varying onset times might result in poor muscle relaxation at the time of intubation even when NMBDs are used (14–16). There are no prospective investigations that systematically evaluated the possible role of monitoring on the incidence and severity of laryngeal injury. Therefore, the current study was designed to assess the impact of monitoring on the incidence and severity of laryngeal morbidity.

The trauma causing laryngeal injury can occur on several occasions: during induction of anesthesia as a direct trauma by the intubation tube, during surgery, or during tracheal extubation (9). Thus, a baseline incidence of VCI may exist independently of the quality of tracheal intubation during the induction of anesthesia (7). Many factors contributed to laryngeal intubation trauma (9), including demographic factors such as sex (3,5), weight (3), history of smoking and gastroesophageal reflux (11), technical factors such as endotracheal tube size (10), type of tube (3), cuff design, cuff pressure, use of introducer (3), and stomach tube, type and duration of surgery (9,12,13), and intubating conditions (7). However, the risk factors for VCI and PH were controlled in the present study (Table 2). Moreover, among other factors, type of tube, and tube size, were standardized. In addition, all intubations were performed by the same experienced anesthesiologist and the patient's head was fixed without neck extension after tracheal intubation (9,13). As the patients underwent surgery of the ear, the head was slightly moved before surgery started. Therefore, this could have been a risk factor for increasing the baseline incidence of VCI.

Intubation-related laryngeal injuries were found to be present in up to 12% of patients with the use of NMBD for tracheal intubation (4,7,21,23) and have been observed in 42% of patients without NMBD (7). In the present study, the incidence of VCI was 27%, mainly consisting of bilateral thickening of the vocal folds (86%). The incidence of VCI (with NMBD) was more frequent than previously described (4,7,21,23). Moreover, unilateral (left) injuries were usually most common (7,21,23), as opposed to bilateral injuries of the vocal cords, and hematomas were usually the most frequent lesions (7,9,21,23), rather than thickening of the vocal folds as in the present study. Only two patients had left VCI, the most frequent type of injury in the previous prospective studies (Fig. 2) (7,21,23). Bilateral injuries of the vocal folds usually occur during insertion of the tracheal tube when the vocal folds are closed or are closing and after insertion of the tracheal tube, when the patient is coughing and the vocal folds beat against the tube. However, in the present study there was no correlation between the incidence and severity of PH and VCI and the intubating conditions or subcomponents.

Surprisingly, 36% of the patients in the monitoring group had VCI and 28% had PH although tracheal intubation was performed at maximum neuromuscular block. However, 52% of the patients in the monitoring group had a maximum T1 depression of <95% at the adductor pollicis muscle. Neuromuscular blockade at the adductor pollicis muscle was poorly correlated with intubating conditions (24). The reason is that the adductor pollicis muscle is more sensitive to NMBD and could be fully paralyzed, whereas complete paralysis at the vocal cords or diaphragm was not obtained (16).

However, intubating conditions are not only influenced by the degree of the neuromuscular blockade but also by the depth of anesthesia (25). Therefore, we assessed HR and MAP after tracheal intubation and compared them with those at baseline and after induction of anesthesia because laryngoscopy and tracheal intubation are noxious stimuli for quantification of clinical depth of anesthesia (26). Hemodynamic variables were comparable between groups except for MAP at postintubation time, which seems not to be of clinical significance.

In conclusion, the present study demonstrated that monitoring improved intubating conditions. However, tracheal intubation after administration of atracurium 0.5 mg/kg at maximum neuromuscular block was not associated with a decrease of VCI compared with a waiting time of 2 minutes. Monitoring should be used if excellent intubating conditions are mandatory.


   Appendix: Assessment of Postoperative Hoarseness (PH) and Sore Throat
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Appendix: Assessment of...
References
 
A. Do you have any hoarseness?

If the answer was no, PH was graded 0 = no hoarseness;

If the answer was yes, PH was graded 1–3 as follows (10):

1 = noticed by patient,

2 = obvious to observer,

3 = aphonia.

B. Do you have any sore throat (ST)?

If the answer was no, ST was graded 0 = no sore throat;

If the answer was yes, ST was graded 1–3 as follows (1):

1 = mild (pain with deglutition),

2 = moderate (pain present constantly and increasing with deglutition),

3 = severe (pain interfering with eating and requiring analgesic medication).


   Footnotes
 
Presented, in part, as an abstract at the EUROANAESTHESIA Congress in Lisbon/Portugal, June 5–8, 2004.

Accepted for publication July 22, 2005.


   References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 Appendix: Assessment of...
 References
 

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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