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Rocuronium Is Not Associated with More Vocal Cord Injuries than Succinylcholine After Rapid-Sequence Induction: A Randomized, Prospective, Controlled Trial

Mencke, Thomas, MD*; Knoll, Heike, MD; Schreiber, Jan-Uwe, MD; Echternach, Matthias, MD; Klein, Sarah, MD; Noeldge-Schomburg, Gabriele, MD*; Silomon, Malte, MD

doi: 10.1213/01.ane.0000194509.03916.02
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Postoperative hoarseness (PH), sore throat (ST), and vocal cord injuries (VCI) are common complications after general anesthesia. Excellent endotracheal intubating conditions are associated with less laryngeal morbidity than good or poor intubating conditions. Thus, we tested the hypothesis that a rapid-sequence induction (RSI) with succinylcholine would lead to less PH and VCI than with rocuronium. In this prospective trial, 160 patients were randomized in 2 groups to receive thiopental 5.0 mg/kg, fentanyl 3.0 μg/kg, succinylcholine 1.0 mg/kg, or rocuronium 0.6 mg/kg during RSI. PH and ST were assessed at 24, 48, and 72 h after surgery, VCI were examined by stroboscopy in those patients who had PH >3 days. Excellent and clinically acceptable intubating conditions were significantly increased in the succinylcholine group compared with the rocuronium group: 57% versus 21% and 89% versus 59%, respectively (P < 0.001). The incidence and severity of PH, and VCI between the succinylcholine and the rocuronium groups did not differ significantly: PH: 50% versus 51% (P = 0.99) and VCI: 3% versus 1% (P = 0.98), respectively. Similar findings were found for ST, 39% versus 28% (P = 0.22), and postoperative myalgia, 39% versus 29% (P = 0.25), respectively. Intubating conditions were significantly better in the succinylcholine group compared with the rocuronium group. The incidence and severity of ST and myalgia were not increased in the patients receiving succinylcholine. However, the rate of PH and VCI was similar to the rocuronium group.

IMPLICATIONS: We tested the hypothesis that a rapid-sequence induction with succinylcholine would lead to less vocal cord injuries than with rocuronium. Intubating conditions were significantly better in the succinylcholine group compared with the rocuronium group. However, the rate of adverse airway effects was not different between groups. Succinylcholine should be used if excellent intubating conditions are mandatory.

*Department of Anaesthesia and Intensive Care Medicine, University of Rostock, Rostock, †Department of Anaesthesia and Intensive Care Medicine, ‡Department of Otorhinolaryngology, University of the Saarland, Homburg/Saar, ∥Department of Anaesthesia and Intensive Care Medicine, Catholic Hospital, Koblenz, Germany

Accepted for publication September 19, 2005.

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

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

Postoperative hoarseness (PH), sore throat (ST), and vocal cord injuries (VCI) are common complications after general anesthesia (1–7). The incidence of PH is as frequent as 50% after short-term tracheal intubation (5). Moreover, 3% of patients had a persistent voice change for more than 6 mo (8). Several risk factors for PH and laryngeal injury have been identified, including technical factors such as endotracheal tube size, as well as demographic factors (2,3,9–13). We demonstrated that 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). A rapid-sequence induction (RSI) can be performed with succinylcholine or rocuronium (14). A meta-analysis by Perry et al. (15) showed that excellent intubating conditions were reached significantly more often when succinylcholine 1.0 mg/kg was used instead of rocuronium 0.6 mg/kg after RSI with thiopental (15). Based on the results of our first study (7) showing that excellent intubating conditions were most likely associated with the least frequent incidence of laryngeal morbidity, we tested the hypothesis that a RSI with succinylcholine would cause less PH and VCI than rocuronium. In addition, is succinylcholine associated with an increased risk for postoperative myalgia (POM) and ST?

Therefore, the purpose of this study was to investigate the incidence and severity of PH, ST, VCI, and POM in patients requiring a RSI after administration of rocuronium 0.6 mg/kg. These data were compared with those after the administration of succinylcholine 1.0 mg/kg.

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Methods

After obtaining approval from the Institutional Review Committee and written informed patient consent, we studied 160 adult ASA physical status I–II patients aged 18–77 yr. All patients underwent orotracheal intubation as a RSI for abdominal surgery. Abdominal surgery patients included those characterized by a full stomach, those at risk for pulmonary aspiration, i.e., patients with gastric or intestinal carcinoma, appendicitis, cholecystitis, or ileus. Patients with a preexisting hoarseness or ST before surgery were not included. Study exclusion criteria included time for surgery >6 h, obesity, pregnancy, 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 possible difficult intubation, i.e., Cormack and Lehane (16) score of 3 or 4 were excluded after induction of anesthesia.

Patients were randomized in 2 groups of 80 patients each via random number draws to receive either succinylcholine 1.0 mg/kg (succinylcholine group) or rocuronium 0.6 mg/kg (rocuronium group). The study drugs were administered in a double-blind fashion and syringes were prepared (adjusted to a 10 mL volume) by an independent investigator.

The induction regimen was standardized in a rapid-sequence manner (with cricoid pressure, with the head-up position) as a “fast technique” (17) for both groups as follows: after 3 min of administration of oxygen, fentanyl 3.0 μg/kg was injected; 4 min later anesthesia was induced with thiopental 5.0 mg/kg. Immediately afterwards, the study drug (succinylcholine or rocuronium) was injected over a period of 5 s. To prevent the anesthesiologist who performed the tracheal intubation from noting succinylcholine-induced muscle fasciculations, he was called to enter the study room after 40 s; exactly 50 s after administration of the neuromuscular blocking drugs (NMBD), and without positive pressure ventilation, laryngoscopy started (using a Macintosh laryngoscope blade size 3); thus approximately 10 s later the trachea was intubated. After successful intubation, a stomach tube was positioned under direct laryngoscopy. The patients were then carefully positioned for surgery and the head was fixed. Anesthesia was maintained with remifentanil 0.25–0.4 μg · kg−1 · min−1, desflurane 3%–4% (end-tidal) in oxygen/air, and bolus doses of rocuronium 0.1–0.3 mg/kg. Twenty minutes before the expected end of surgery, all patients received piritramide 3.0 mg IV, which is a synthetic opioid with pharmacodynamic properties similar to morphine. After surgery, piritramide 0.05 mg/kg IV was given by request, and thereafter paracetamol was also given. At the end of surgery tracheas were extubated and the patients were moved to the postanesthesia care unit (PACU).

Tracheal intubation was performed by the same experienced anesthesiologist. 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 following intubating variables were recorded: glottic exposure as defined by Cormack and Lehane; the number of intubation attempts (n); time to intubation (s), defined as the time from the end of administration of the NMBD until removing the laryngoscope from the patient’s mouth after successful intubation. The following factors were standardized for all patients: tube size (men: inner diameter, 8.0 mm; women: inner diameter, 7.0 mm), type of tube (Magill, Lo-Contour™ Murphy Tracheal Tube; Mallinckrodt, Athlone, Ireland), use of a stylet (limited to the edge of the tracheal tube), use of lidocaine gel 2%, and intracuff pressure <30 mm Hg (measured with a noninvasive manometer).

Table 1

Table 1

PH was defined as an acoustic quality that was different than the previous voice quality of the patient (19). ST was defined as continuous throat pain (2). An investigator blinded as to the group assignment of the patients asked the patients specific questions concerning PH, ST, and POM in the PACU and on days 1, 2, and 3 after surgery (1,9,20,21) (Appendix). A daily follow-up examination was performed until complete resolution.

VCI were assessed by laryngostroboscopy by an experienced ear-nose-throat physician who was unaware of the patient’s group assignment. All patients with a PH lasting longer when 3 days underwent a stroboscopic examination of the vocal cords. VCI were assessed as follows (7,10,22): location: unilateral (left or right vocal cord) or bilateral (both vocal cords); type of injury: thickening of the vocal folds, edema, erythema, hematoma, granuloma. Follow-up examination was performed until complete resolution.

Statistical analysis was performed using the SigmaStat® for Windows 2.0 statistical software (Jandel Corporation, San Rafael, CA). The required number of patients for the study groups was calculated in expectation of an incidence of PH of 16% (7) in the succinylcholine group and a 20% increase of the absolute risk in the rocuronium group. For an 80% power and an α = 0.05, 150 patients (75 patients in each group) were needed. To compensate for possible drop-outs, we enrolled 160 patients, i.e., 80 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 χ2 test or Fisher’s exact test and one-way analysis of variance as appropriate.

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Results

One-hundred-sixty patients were enrolled in this study: 80 patients in each group. Of these 160 patients, 10 patients were excluded from analysis (Fig. 1). There were no significant differences between the two groups with respect to demographic data and duration of anesthesia (Table 2).

Figure 1.

Figure 1.

Table 2

Table 2

Tracheal intubation was successful in all patients of both groups. Time of intubation, number of attempts, and Cormack and Lehane grades did not differ significantly between study groups. The rate of excellent intubating conditions was significantly more frequent in the succinylcholine group compared with the rocuronium group: 42 (57%) versus 16 patients (21%), respectively (P < 0.001). Similar results were noted for clinically acceptable (excellent and good) intubating conditions: 66 (89%) versus 45 patients (59%), respectively (P < 0.001). Results concerning the subcomponents are shown in Figure 2.

Figure 2.

Figure 2.

The overall incidence (succinylcholine and rocuronium groups together) of PH was 51% (76 patients). PH did not differ significantly between groups: 37 patients (50%) versus 39 patients (51%), respectively (P = 0.998) (Table 3). In 8 patients (5.3%) (4 patients of each group) PH lasted longer than 3 days. Follow-up examination revealed that 4 patients (2.7%) suffered from PH >7 days (Table 3). The severity of PH did not differ significantly between study groups.

Table 3

Table 3

Stroboscopic examination was performed in all 8 patients suffering from PH >3 days. Among these 8 patients 3 patients (2 succinylcholine versus 1 rocuronium patient; P = 0.981) had VCI. All VCI were unilateral (right/left vocal cords = 2/1) and consisted of 1 hematoma, 1 edema, and 1 granuloma. Follow-up examination revealed that this granuloma (succinylcholine group) persisted for 1 wk (Fig. 3).

Figure 3.

Figure 3.

The overall incidence (both study groups together) of ST was 33% (50 patients). ST did not differ significantly between groups: 29 patients (39%) versus 21 patients (28%), respectively; P = 0.224 (Table 3). The severity of ST did not differ significantly between study groups.

Overall 11 patients (7.3%) suffered from laryngeal morbidity lasting longer than 3 days (PH, 8 patients; ST, 3 patients; VCI, 3 patients). Among them one patient experienced PH for 11 days (hematoma), one for 9 days (edema), and another for 7 days (granuloma of the vocal folds) (Fig. 3).

The relation between the intubating conditions and PH is shown in Figure 4. In the succinylcholine group 21 of 42 patients with an excellent intubating score were hoarse (50%), 10 of 24 patients with good intubating scores were hoarse (42%), and 6 of 8 patients with poor intubating scores were hoarse (75%) (P = not significant). Similar findings were observed in the rocuronium group: 9 of 16 patients with excellent intubating scores were hoarse (56%) compared with 14 of 29 patients with good scores (48%) and 16 of 31 patients with poor intubating scores (52%) (P = not significant).

Figure 4.

Figure 4.

Between the succinylcholine and rocuronium groups, there was no significant difference concerning the incidence (29 versus 22 patients, respectively; P = 0.250) and severity of POM (Table 4). Bradycardia requiring atropine IV occurred in 6 patients (3 in each group; P = 0.701). No severe bradycardia or arrhythmia was observed.

Table 4

Table 4

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Discussion

The present study demonstrated that the rate of excellent and clinically acceptable intubating conditions during a RSI was significantly more frequent in the succinylcholine group compared with the rocuronium group. In addition, succinylcholine was not associated with more frequent incidence and severity of ST and POM. However, the incidence and severity of PH and VCI was similar compared with the rocuronium group.

Many factors contribute to laryngeal intubation trauma (10). Several risk factors for VCI and PH have been identified, including demographic factors such as sex (3) and gastroesophageal reflux (11), technical factors such as endotracheal tube size (9), use of an introducer (3), stomach tube (23), type, and duration of surgery (10,12,13), and the intubating conditions (7). Risk factors known to contribute to PH and VCI were controlled in the present study. The patient population was uniform with respect to the patient characteristics, as well as to the type and duration of surgery (Table 2). Moreover, type of tube, and tube size were standardized (men got a tracheal tube with an inner diameter of 1.0 mm larger than women).

We (7) demonstrated that excellent intubating conditions were less frequently associated with PH and VCI compared with good or poor conditions. In the present study, however, we did not confirm these results. In the group receiving rocuronium 0.6 mg/kg the quality of tracheal intubation was significantly worse than in the group receiving succinylcholine 1.0 mg/kg. In contrast to our first study (7), laryngeal morbidity was not significantly affected by the intubating conditions (Fig. 4). There was no correlation between the incidence and severity of PH or VCI and the intubating conditions or subcomponents. In the first study (7) the saline group received no NMBD; in the present study all patients received a NMBD (rocuronium or succinylcholine). The incidence of poor intubating conditions was 33% (saline group) versus 5% (atracurium group) in the first study, and 11% (succinylcholine) versus 41% (rocuronium) in the present study. The Copenhagen scoring system defines sustained coughing as poor intubating conditions. We suppose that coughing could be different with regard to intensity and therefore lead to different rates of PH, and VCI. However, a baseline incidence of PH and VCI may exist independently of the quality of tracheal intubation during the induction of anesthesia. In the first study the patients underwent surgery of the ear (7) and the head was only slightly moved. In contrast, in the present study the head was fixed after tracheal intubation but the neck was extended during positioning to facilitate laparotomy. This might increase PH and VCI, as known from cardiac surgery (13). In contrast to our first study (7), a stylet was used, a stomach tube placed, and cricoid pressure applied. Turgeon et al. (24) randomized 700 patients to have a standardized cricoid pressure or a sham cricoid pressure. Cricoid pressure applied by trained personnel did not increase the rate of failed intubation. Moreover, the grades of laryngoscopic view and the intubation difficulty scale score were also comparable (24). The results of their study are in contradiction to the common clinical assumption that cricoid pressure impedes visualization of the larynx and with case reports of difficult intubation. In our study only trained anesthesia personnel took part in the study. However, patients with a Cormack and Lehane grade 3 or 4 were excluded after induction of anesthesia. It was standardized that we used a stylet for all patients, but they were limited to the edge of the tracheal tube. An evaluation of the gum elastic bougie (25) showed no increased incidence of hoarseness; the use of an introducer was associated with a longer PH (3). In one case report, a stomach tube was associated with an increased incidence of ST, postcricoid inflammation, and vocal cord immobility (23). These risk factors together might have increased the baseline incidence of PH and therefore the risk factor “poor intubating conditions,” i.e., inadequate muscle relaxation lost its impact on PH in the current study.

There is a large variation in the reported incidence (3%–50%) of PH immediately after short-term tracheal intubation (3–5,7,8). Oczenski et al. (4) reported an incidence of PH of 44% after rocuronium 0.6 mg/kg (the same dosage as in our study). This frequent incidence can be explained by the relatively large size of tracheal tubes that were used (4). Tracheal intubation with atracurium 0.5 mg/kg 3 minutes after induction of anesthesia was associated with an infrequent incidence of PH of 16% (7). Moreover, PH was limited to the PACU and VCI resolved within 72 hours (7). In our current study, however, the overall incidence of PH was as frequent as 51%. Furthermore, at 72 hours almost 9% of the patients were still hoarse, and after 1 week even 3% of the patients suffered from hoarseness (Table 3).

Intubation-related laryngeal injuries were found to be present in up to 12% of patients with the use of NMBD for tracheal intubation (4,7,22,26) and reached 44% in patients with an induction technique without NMBD (7). In the study conducted by Kambic and Radsel (26) in 1000 patients after tracheal extubation using the indirect mirror examination, the incidence of direct lesions was 6.2%. These results were confirmed by Peppard and Dickens (22), who found traumatic lesions in 6.3% of the patients. These studies were done nearly 25 years ago; different tube type or cuff design might lead to different results today. In our study, only patients with a PH lasting longer than 72 hours were examined by laryngostroboscopy. All VCI were unilateral suggesting direct trauma by intubation (22,26). Follow-up examinations revealed that 1 patient in the succinylcholine group had persistent granuloma at the right vocal cord for 1 week (Fig. 3). The infrequent incidence (2%) of VCI in our study could be explained by the design of the study, i.e., patients were examined on the fourth day after surgery, when they were still hoarse. Presumably, most minor injuries of the vocal folds, such as edema, thickening of the vocal folds, or hematoma, might have been resolved in the first 24 or 48 hours after surgery.

ST varies between 14.4%–50% (2,4,5,9). Even in unintubated patients, ST occurred when an ordinary facemask was used (1). These findings have been confirmed by another study (6); others found no effect of succinylcholine on ST (5). In the present study, however, the overall incidence of ST was 33%, being comparable between both study groups (Table 3). The mechanism of postoperative ST is not clear, but it was suggested that succinylcholine could induce muscle pain, i.e., myalgia, in the striated pharyngeal muscles (1,2). POM is characterized by succinylcholine-induced myalgia and other causes (21).

In conclusion, intubating conditions were significantly better in the succinylcholine group compared with the rocuronium group. However, the rate of adverse airway effects was not different between drugs. Succinylcholine should be used if excellent intubating conditions are mandatory.

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Appendix: Assessment of Postoperative Hoarseness, Sore Throat, and Postoperative Myalgia

  1. Postoperative hoarseness (PH)
  2. 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 (9):
    1 = noticed by patient
    2 = obvious to observer or
    3 = aphonia.
  3. Sore throat (ST)
  4. Do you have any sore throat?
    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).
  5. Postoperative myalgia (POM)
  6. 1. Do you have any pains and aches or stiffness in your muscles other than the pain where the surgery took place?
    2. If the answer was no, myalgia was graded 0 = none (no pain).
    3. If the answer was yes, POM was graded 1–3 as follows (20,21):
    a. If the pain was confined to one site, myalgia was graded 1 = slight (pain confined to one site but causing no disability).
    b. If the pain was affecting more than one site, myalgia was graded 2 = moderate or 3 = severe.
    c. Does the muscle pain restrict your normal activity?
    i. If the answer was no, myalgia was graded 2 = moderate (pain affecting more than one site but causing no disability).
    i. If the answer was yes, myalgia was graded 3 = severe (pain affecting more than one site and resulting in an inability to get out of bed or cough without distress, or turn the head).
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