Tracheal Intubation with Rocuronium Using the "Timing Principle"

Abstract

We compared the endotracheal intubating conditions after rocuronium, using the "timing principle," with those after succinylcholine.The timing principle entails administration of a single bolus dose of nondepolarizing muscle relaxant, followed by an induction drug at the onset of clinical weakness. Forty-five patients were randomly assigned to three groups. Patients allocated to Groups 1 and 2 received rocuronium 0.6 mg/kg. At the onset of clinical weakness (onset of ptosis), anesthesia was induced with thiopental 4-6 mg/kg; intubation was accomplished after 45 s in Group 1 and after 60 s in Group 2. Patients in Group 3 received vecuronium (0.01 mg/kg) 3 min before the administration of thiopental and succinylcholine 1.5 mg/kg, and their tracheas were intubated 60 s later by a blind anesthesiologist. Intubating conditions were assessed according to a grading scale and were either good (5 patients in Groups 1 and 2, 4 patients in Group 3) or excellent (10 patients in Groups 1 + 2, 11 patients in Group 3) in all patients. Patients were interviewed postoperatively, and all were satisfied with the induction of anesthesia. We conclude that rocuronium 0.6 mg/kg provides good to excellent intubating conditions 45 and 60 s after the induction of anesthesia using the timing principle. Implications: We compared the ease with which a breathing tube could be placed in patients using three techniques. The standard technique (succinylcholine) was compared with two others in which a musclerelaxing drug (rocuronium) was administered just before the anesthetic drug (so-called timing principle). No difference among the techniques was observed.

(Anesth Analg 1998;86:1137-40)

One characteristic of the ideal muscle relaxant is a rapid onset of action. Succinylcholine reliably produces muscle relaxation within 60 seconds of its administration, but it can produce serious side effects ^[1-5] and is contraindicated in certain patients ^[6]. Different techniques that have been used to decrease the effective onset time of nondepolarizing muscle relaxants include priming ^[7] and the administration of large doses ^[8]. Recently, a technique that uses the "timing principle" has been applied to rapidly produce good intubating conditions with vecuronium ^[9,10] and atracurium ^[11]. When this technique is used, a single bolus dose of a muscle relaxant is administered, and anesthesia is induced at the onset of clinical weakness. In this way, the time from the induction of anesthesia to complete muscle relaxation is reduced, and the peak effect of the muscle relaxant and IV induction drug may more closely coincide. Rocuronium is a steroidal nondepolarizing muscle relaxant with an onset time (after 3-4 x the 95% effective dose) not different from that of succinylcholine ^[12-16]. In a prospective, randomized, double-blind clinical trial, we evaluated the intubating conditions 45 and 60 s after the induction of anesthesia using rocuronium with the timing principle, and compared them with those after the administration of succinylcholine 60 s after the induction of anesthesia.

Methods

With institutional ethical committee approval, and after having obtained written, informed consent from each, 45 ASA physical status I or II patients (18-70 yr) undergoing elective surgical procedures were studied. Exclusion criteria were: increased risk of pulmonary aspiration, neuromuscular disease, medications known to influence neuromuscular function, anticipated difficulty with airway management, and contraindications to succinylcholine.

The usual monitoring was used. Neuromuscular function was measured using accelerography (TOF-Guard[registered sign]; Organon Teknika, Durham, NC). Patients were informed that they might feel weak before going to sleep.

All patients received midazolam (1-3 mg) and fentanyl (1 [micro sign]g/kg) IV on arrival in the operating room. Patients were randomly assigned to one of three groups: rocuronium 45s (Group 1), rocuronium 60s (Group 2), and succinylcholine (Group 3). Cutaneous electrodes were placed for measurement of the train-of-four (TOF) response of the first dorsal interosseous muscle of the hand to stimulation of the ulnar nerve.

Patients allocated to Groups 1 and 2 received rocuronium (0.6 mg/kg) administered over 5 s through a rapidly running infusion placed in the forearm. Patients were asked to keep their eyes widely open as long as possible and were closely observed for the first signs of weakness, specifically the onset of ptosis (i.e., furrowing of the forehead, which indicates that the occipitofrontalis muscle is being used to compensate for neuromuscular weakness of the levator palpebrae superioris muscle). At this time, thiopental (4-6 mg/kg) was administered IV. TOF monitoring was commenced on loss of the eyelid reflex. Supramaximal square wave stimuli were applied to the ulnar nerve at 2 Hz for 2 s (i.e., TOF stimulation). This was repeated at 10-s intervals until no response was detected. After the administration of thiopental (45 s in Group 1 or 60 s in Groups 2 and 3), the TOF count was recorded, and tracheal intubation was performed by an experienced anesthesiologist unaware of the group to which the patient belonged. This person was waiting outside the induction area and did not enter until the patient was ready for intubation. Intubating conditions were assessed according to a previously described grading scale (Table 2) ^[9]. In addition, a second blind observer observed the abdomen for evidence of diaphragmatic response to endotracheal intubation. On capnographic confirmation of correct tube placement, controlled positive pressure ventilation was commenced using 70% nitrous oxide in oxygen (6 L/min fresh gas flow) and isoflurane (inspired concentration 1%-1.5%).

Table 2: Demographic Data and Thiopental Doses

Patients in Group 3 (succinylcholine) were treated according to the protocol described for those in Groups 1 and 2 with the following exceptions. Three minutes after the administration of a defasciculating dose of vecuronium (0.01 mg/kg), thiopental (4-6 mg/kg) and succinylcholine (1.5 mg/kg) were administered in succession over 5 s. Sixty seconds after administration of thiopental, tracheal intubation was performed. TOF monitoring was not performed in Group 3.

All patients were interviewed by the investigator (nonblinded) 4-24 h after the surgical procedure. Four questions were asked:

1. Did you feel weak immediately before going to sleep for your operation?

2. Did you feel short of breath immediately before going to sleep for your operation?

3. Do you have muscle pains now?

4. If you were to have an operation in the future, would you choose to be put to sleep in a different way?

Age, body weight, sex, thiopental doses (all three groups), and time to clinical onset of neuromuscular blockade (Groups 1 and 2 only) were compared by using one-way analysis of variance when data were normally distributed; otherwise, the Kruskal-Wallis one-way analysis of variance on ranks was used. Normality of distribution of the data was checked by using the Kolmogorov-Smirnov test ^[17]. A P value <0.05 was considered statistically significant. The statistical package used was Sigma Stat, version 2.0 (Jandel Corporation, San Rafael, CA).

Results

There were no significant demographic differences among groups with respect to age and weight, but there were significantly more female patients in Group 3 compared with Groups 1 and 2. There was no statistically significant difference in the thiopental doses of the three groups (Table 1). Tracheal intubation score results (all three groups) and TOF counts at the time of intubation (Groups 1 and 2 only) are summarized in Figure 1 and Table 3. Intubating conditions were either good or excellent in all patients. The mean (+/- SD) onset time to clinical weakness was not different in the two rocuronium groups: 32 +/- 4.9 s in Group 1 and 32 +/- 5.3 s in Group 2.

Table 1: Grading of Intubating Conditions (Intubation Score)

Figure 1: Intubating conditions. Intubation scores: 3 = excellent (jaw relaxed, cords abducted, no movement), 2 = good (jaw relaxed, slight cough), 1 = poor (jaw poorly relaxed, cords moving or bucking), 0 = unable to intubate.

Table 3: TOF Count Immediately Before Endotracheal Intubation

In the postoperative interview, none of the patients complained about weakness or shortness of breath before induction of anesthesia, and only one patient in Group 3 (succinylcholine) experienced postoperative muscle pain. All patients were satisfied with the manner in which anesthesia had been induced.

Discussion

Using the timing principle, the administration of rocuronium (0.6 mg/kg) resulted in adequate intubating conditions 45 seconds after the induction of anesthesia or approximately 77 s after the injection of the muscle relaxant. All patients found the manner in which anesthesia had been induced to be acceptable. Using the timing principle with rocuronium, it is possible to reduce the interval between induction of anesthesia and intubation of the trachea to <60 s.

Such a technique is desirable because of the significant side effects associated with the use of succinylcholine ^[1-5]. Alternative strategies to reduce the onset time of nondepolarizing muscle relaxants, such as priming ^[7] and administering large doses ^[8], have not been completely successful. The objective of the use of the timing principle is not to increase the speed of onset of the muscle relaxant, but to induce muscle relaxation and general anesthesia simultaneously rather than sequentially.

When the timing principle is used, the initial signs of clinical weakness precede loss of consciousness. A potential risk, therefore, is that patients would experience an uncomfortable feeling during the induction sequence. In our study, no patient demonstrated restlessness at the time that ptosis was observed. This suggests that patient satisfaction with the manner in which they went to sleep (in response to the postoperative questionnaire) was not because of amnesic effects of anesthetics, but because the degree of muscle weakness present was not associated with discomfort. Debaene et al. ^[18] demonstrated that onset of neuromuscular blockade in the diaphragm was similar to that in orbicularis oculi but faster than that in adductor pollicis. Koh and Chen ^[11] also used ptosis (rather than handgrip strength) as the marker for the onset of clinical weakness, postulating that onset time for neuromuscular block at levator palpebrae superioris would be similar to that in orbicularis oculi and, therefore, that in the diaphragm. In Koh and Chen's ^[11] study of the use of the timing principle with atracurium (0.5, 0.75, or 1.0 mg/kg), only one patient expressed dissatisfaction with the anesthetic technique used, and three felt discomfort. It is unlikely that the absence of such complaints in our study was due to a pharmacodynamic effect of rocuronium, because the times to onset of clinical weakness in our study (32 +/- 4.9 and 32 +/- 5.3 s) were similar to those after atracurium (32 +/- 9.3, 29 +/- 1.0, and 28 +/- 11.7 s). It is more likely due to the administration of midazolam and fentanyl before the muscle relaxant.

Because of the rapid speed of onset of neuromuscular block after rocuronium and the narrow range of standard deviation in the time to onset of clinical weakness (32 +/- 4.9 and 32 +/- 5.3 s), another approach of the timing principle might be not to wait for the onset of clinical weakness, but to induce anesthesia after a fixed interval, e.g., 20 s after the administration of rocuronium. Further studies are needed to address a safe time interval.

There are several reports about pain on injection of rocuronium ^[19], even in subparalyzing doses. In our study, only 5 of 30 (16.7%) patients who received rocuronium withdrew their forearm during the injection of rocuronium. This withdrawal was interpreted as a reaction to a painful stimulus. Because the issue of pain on injection was not actually raised until the study was under way, we had not included any questions concerning this problem specifically in the post-operative interview. Nevertheless, none of the patients complained postoperatively about a uncomfortable event during the induction of anesthesia. A possible explanation is the prior administration of midazolam and fentanyl, which has been used to reduce pain on injection ^[20], plus the fact that the IV cannulas were placed in the forearm and not in the small veins of the back of the hand.

Pulmonary aspiration of gastric contents has been associated with a priming dose of vecuronium ^[21,22]. This may be attributable in part to the rapid speed of onset of the muscle relaxant at the adductor muscles of the larynx, compared with that at the adductor pollicis. A similar potential risk may exist when the timing principle technique is used. Indeed, anxiety associated with sensation of weakness or the application of cricoid pressure might result in vigorous inspiratory efforts when airway protective reflexes are compromised, further increasing the risk of pulmonary aspiration. The current study did not address the adequacy of protective reflexes at the onset of clinically detectable weakness. Grading cough as absent, weak, or normal, Koh and Chen ^[11] identified only 1 patient of 60 studied in whom cough was weak at the onset of ptosis.

We conclude that rocuronium 0.6 mg/kg consistently provides good to excellent intubating conditions 45 and 60 seconds after the induction of anesthesia using the timing principle.

The authors thank Yolanda Loffel, CRNA, and Margrit Rindlisbacher, CRNA, for their help and cooperation.