Abstract

Background

Residual neuromuscular blockade (RNMB) is known to be associated with respiratory complications in the postoperative period after muscle relaxant usage. The authors hypothesized that RNMB causes reductions in pulmonary function test (PFT) parameters in the immediate postoperative period.

Methods

An open-label prospective randomized cohort study was conducted comparing reductions in PFT parameters due to RNMB among different neuromuscular blocking agents. One hundred and fifty patients were randomized to receive vecuronium, atracurium, or rocuronium. After reversal of neuromuscular blockade and extubation, train-of-four ratio was measured every 5 min until the train-of-four ratio of 0.9 or greater was attained. PFTs were performed preoperatively and postoperatively when the patients were willing and fit. The train-of-four ratio, measured at PFT, was used to classify patients into “RNMB absent” and “RNMB present.” RNMB was defined as a train-of-four ratio less than 0.9.

Results

Thirty-nine patients had RNMB at the time of performing PFT. There was no statistically significant difference in the postoperative reductions in PFT parameters in patients with RNMB among different neuromuscular blocking agents. Patients were regrouped as RNMB absent and RNMB present, irrespective of neuromuscular blocking agents. Postoperative PFT values for the RNMB-absent and RNMB-present groups were 62% and 49% of baseline forced vital capacity and 47% and 38% of baseline peak expiratory flow of the baseline, respectively. Postoperative forced vital capacity and peak expiratory flow values of RNMB-present patients were lower by 13% and 9% in absolute terms (P < 0.008) and 21% and 19% in relative terms, respectively, compared with RNMB-absent patients.

Conclusion

RNMB results in reductions in forced vital capacity and peak expiratory flow in the immediate postoperative period indicating impaired respiratory muscle function.

• Residual neuromuscular blockade is known to be associated with respiratory complications in the postoperative period after muscle relaxant usage

• Residual neuromuscular blockade after the use of vecuronium, atracurium, or rocuronium results in reductions in forced vital capacity and peak expiratory flow in the immediate postoperative period, indicating impaired respiratory muscle function

Postoperative respiratory impairment may be due to various causes, which include patient factors like obesity and surgical factors like site of incision, tight dressings, gastric dilatation, postoperative pain, and effects of residual anesthetics.1,2  All these factors can result in critical respiratory events like upper airway obstruction, pulmonary aspiration, atelectasis, and pneumonic consolidation.

Despite using reversal agents at the end of surgery and clinically apparent return of neuromuscular function, residual neuromuscular blockade (RNMB) is known to occur in the postanesthesia care unit (PACU).3–5  RNMB may be a major cause of respiratory weakness in the immediate postoperative period, resulting in a restrictive respiratory pattern. Several recent volunteer and clinical studies have shown that RNMB is associated with respiratory complications.6–9  However, despite a growing body of evidence establishing the clinical importance of RNMB, there are no data quantifying the impact of RNMB on pulmonary function in the immediate (first hour) postoperative period.

We hypothesized that RNMB causes reduction in pulmonary function in the immediate postoperative period. The reduction in postoperative pulmonary function parameters was compared between patients with and without RNMB among different neuromuscular blocking (NMB) agents.

Materials and Methods

Study Design and Participation

One hundred and fifty patients of either sex, American Society of Anesthesiologists grades 1 and 2, aged 18–60 yr, coming for elective surgeries lasting for less than 3 h, requiring intraoperative neuromuscular blockade were recruited for a single-center open-label prospective randomized cohort study. Written informed consent was taken from patients. Data were collected for a 2-yr period (July 2008–June 2010) at Manipal Hospital (a corporate tertiary care center with postgraduate training program), Bangalore, Karnataka, India. The study was approved by the institutional review board (Hospital Ethics Committee for Human Research, Manipal Hospital, Bangalore, Karnataka, India), which supervised the data collection and safety issues.

Exclusion criteria were patients with cardiorespiratory abnormalities (New York Heart Association heart failure grades 3 and 4, bronchial asthma, chronic obstructive pulmonary disease, and restrictive lung disease), renal insufficiency (serum creatinine more than 1.6 mg/dl), liver dysfunction (liver enzymes—serum glutamic oxaloacetic transaminase/serum glutamic pyruvic transaminase values elevated by more than 50% of normal), underlying neuromuscular disease, the use of drugs known to interfere with neuromuscular transmission, intraoperative hypothermia (core temperature less than 35°C), history of smoking, thoracic and upper abdominal surgeries, unwillingness to perform pulmonary function test (PFT), and severe obesity (body mass index greater than 35).

Preoperative PFT Measurements

During preanesthesia evaluation, all the patients were familiarized using a spirometer. Baseline PFT was performed, with patients in erect sitting posture and a nose clip attached, using MicroplusTM gold standard pocket spirometer, Micromedical (Care Fusion, Rochester, Kent, United Kingdom). They were made to inhale maximally to total lung capacity and exhale maximally through the mouthpiece with lips closed around the mouthpiece. Three consecutive readings were recorded, and the best set of values was noted. Forced vital capacity (FVC), peak expiratory flow (PEF), respiratory rate, and oxygen saturation were recorded.

Patients were informed about the train-of-four (TOF) measurements that would be performed postoperatively, the possible discomfort or pain associated with it, and the PFT that would be performed once more during the postoperative period. All patients were premedicated with intramuscular glycopyrrolate 0.2 mg half an hour before surgery.

Intraoperative Management

A computer-generated simple 1:1:1 randomization table (created using Microsoft Excel 2003 software, Redmond, WA) was used to allocate the muscle relaxant (vecuronium, atracurium, or rocuronium) to be used intraoperatively. This was revealed to the anesthesiologist just before entering the operating room. Standard intraoperative monitoring included electrocardiography, capnography, noninvasive blood pressure, pulse oximetry, and nasopharyngeal temperature. Neuromuscular monitoring was not performed during the intraoperative period. Anesthesia was induced with 1.5 mg/kg propofol, 2 μg/kg fentanyl, and 1.5 mg/kg lidocaine. For muscle relaxation, patients received either vecuronium (0.10–0.15 mg/kg), atracurium (0.5 mg/kg), or rocuronium (0.6–0.8 mg/kg).

Anesthesia was maintained with 0.6–1.2% isoflurane in 50% oxygen and nitrous oxide mixture to maintain mean blood pressure within 20% of the baseline values. Analgesia was maintained by fentanyl (1 μg⋅kg−1⋅h−1 boluses). The maintenance of muscle relaxation, either by top-up doses or infusions, was left to the discretion of the consultant anesthesiologist managing the patient. For the maintenance of muscle relaxation, patients received one of the three relaxants: vecuronium, 0.02 mg/kg top-up doses every 20–30 min or 0.05 mg⋅kg−1⋅h−1 continuous infusion; atracurium, 0.1 mg/kg top-up doses every 20 min or 0.3 mg⋅kg−1⋅h−1 continuous infusion; or rocuronium, 0.15 mg/kg top-up doses every 30 min or 0.3 mg⋅kg−1⋅h−1 continuous infusion. Ventilation was controlled to maintain end-tidal carbon dioxide between 30 and 35 mmHg. Normothermia was maintained using forced air warming with Level1TM (Smith Medical Inc., Rockland, MA). All the patients received neostigmine 0.05 mg/kg and glycopyrrolate 0.01 mg/kg at the end of the surgery for reversal of neuromuscular blockade. Patients were extubated on the basis of clinical judgment of the anesthesiologist managing the case. Total dose of NMB agents used, time of administration of NMB agent at induction, time of administration of the last dose of NMB agent/stoppage of infusion, time of administration of reversal agent, and time of extubation were noted.

TOF and PFT Measurements in PACU

On arrival at the PACU, all patients received 5 l/min O2via mask and were monitored with electrocardiography, pulse oximeter, and noninvasive blood pressure. Neuromuscular monitor (TOF watch®; Organon Ltd., Dublin, Ireland) was applied to all the patients. The acceleration transducer was attached to the volar aspect of the interphalyngeal joint of the thumb to sense the contraction of adductor pollicis muscle. The two surface electrodes were placed over the ulnar aspect of the wrist, the stimulating electrode over the ulnar nerve at the crease of the wrist, and the other electrode 4 cm proximal to it. The arm and fingers were immobilized using a splint, and free movement of the thumb was ensured. After an uncalibrated TOF stimulation (four pulses of 0.2-ms duration for 2 s at a frequency of 2 Hz; current intensity, 50 mA), which was repeated four to five times at an interval of 12 s between stimulations, the highest of the two consecutive reproducible TOF ratio was noted. TOF measurements were repeated every 5 min until a TOF ratio of 0.9 or more was reached.

Patients were also checked every 5 min to see whether they were awake, alert, and willing to perform PFT. Once they were ready, three consecutive PFT readings were recorded in propped up position (back reclined at 45° with knee flexion of 20°–30°), and the best set of values was noted. During the postoperative period, Spo2% and respiratory rate were noted. Patients were monitored by an observer for adverse respiratory events like hypoxia (Spo2 less than 90%), shallow rapid breathing (respiratory rate higher than 30 breaths per minute), upper airway obstruction requiring nasopharyngeal or oropharyngeal airway, stridor, laryngospasm, inability to swallow, or pulmonary aspiration.

Time of first TOF reading (baseline), time of attaining a TOF ratio of 0.9 or more, and time of performing postoperative PFT were noted. The TOF ratio at PFT was also noted. If the patient had already attained a TOF ratio of 0.9 or more before performing PFT, then the TOF measurement was not repeated and the last measured TOF ratio was taken as the “TOF at PFT.” In patients who still had not attained a TOF ratio of 0.9 at the time of performing PFT, the TOF measurement was repeated until a TOF ratio of 0.9 or more was attained. The TOF ratio less than 0.9 was used to define residual paralysis. Patients were divided into two groups, RNMB present (TOF less than 0.9) and RNMB absent (TOF ≥ 0.9), based on the TOF ratio at PFT.

On the basis of the timings noted, various time intervals were calculated. The time intervals included the duration of neuromuscular blockade (time from administration of NMB agent at induction to administration of reversal agent), the reversal to attaining a TOF ratio of 0.9 or more, the reversal to postoperative PFT, and a TOF ratio of 0.9 or more to postoperative PFT.

Plan of Analysis

The various study variables including demographic data, time intervals, and PFT parameters were compared among the three groups of patients receiving vecuronium, atracurium, and rocuronium. Next, the study variables between patients with and without RNMB both within and across the vecuronium, atracurium, and rocuronium groups were compared. Finally, all the patients were pooled and classified based on the presence or absence of RNMB, irrespective of the muscle relaxant used as RNMB-present and RNMB-absent groups and compared (fig. 1).

Fig. 1.

The plan of analysis used in the study. The patients were randomized into three primary groups based on the neuromuscular blocking agent received, as vecuronium, atracurium, and rocuronium groups and were compared. Each primary group was subdivided based on presence or absence of RNMB, and the subgroups were compared within and across the primary groups. Further, identical subgroups from all three primary groups were pooled and regrouped as RNMB-present and RNMB-absent groups and were compared. RNMB = residual neuromuscular blockade.

Fig. 1.

The plan of analysis used in the study. The patients were randomized into three primary groups based on the neuromuscular blocking agent received, as vecuronium, atracurium, and rocuronium groups and were compared. Each primary group was subdivided based on presence or absence of RNMB, and the subgroups were compared within and across the primary groups. Further, identical subgroups from all three primary groups were pooled and regrouped as RNMB-present and RNMB-absent groups and were compared. RNMB = residual neuromuscular blockade.

For comparison of PFT parameters, four sets of values of both FVC and PEF were compared. First, preoperative values were compared. Predicted values for FVC and PEF were derived from the nomogram provided by MicroplusTM gold standard pocket spirometer, Micro medical, using age, sex, and height of individual patients. Preoperative values as percentage of predicted FVC or PEF were calculated (% predicted = [preoperative value/predicted value] × 100) and compared. Next, postoperative values were compared. Finally, postoperative values as percentage of preoperative values were calculated (postoperative value as % of preoperative value = postoperative value/preoperative value × 100) and compared.

The primary outcome we planned to study was to compare postoperative FVC and PEF reductions in patients with RNMB following the use of three different intermediate-acting NMB agents. A reduction of 15% or more in FVC or PEF in patients with RNMB compared with patients without RNMB was deemed to be clinically significant, as many clinically used pulmonary risk assessment scales use 15% difference in PFT parameters to grade the severity of pulmonary insufficiency.10,11

Sample Size

As data for PFT parameters in the immediate postoperative period were not available in the literature, sample size could not be estimated based on FVC or PEF. Instead, sample size estimation was performed based on the expected incidence of RNMB postoperatively. A previous meta-analysis showed a mean incidence of RNMB as 0.54 (95% CI, 0.36–0.73) in nonmonitored (intraoperative TOF monitoring) patients who received intermediate-acting muscle relaxants.12  Group size was determined by using the “sample size estimation for proportions” method, with an expected proportion of 0.54 and a two-tailed width of the CI of 0.185 assuming a 95% confidence level. On the basis of this, we estimated that 28 patients were required to be studied in each group. We studied 50 patients in each group (a total of 150 patients) to compensate for the patients who would be lost because of recovery from RNMB before they could perform PFT. We assumed that 40–50% of patients, who would have been classified as having RNMB on arrival to PACU, would continue to have RNMB if PFT is performed within 30 min postoperatively. From our initial clinical experience of performing PFTs postoperatively, we knew that majority of the patients could perform PFT within 30 min.

Statistical Methods

Normally distributed continuous data are presented as mean ± SD. Continuous data, which are not distributed normally, are presented as median (interquartile range). P value less than 0.05 was considered statistically significant. Statistical analysis was performed using the Statistical Package for the Social Sciences (Version 15.0; IBM corporation, Armonk, NY). For comparing different NMB agents with regard to demographic data, PFT parameters, and other study variables, ANOVA or chi-square test were used. Student t test for independent samples was used to compare demographic data, PFT parameters, and other study variables between RNMB-present and RNMB-absent patients. Paired samples Student t test was used to compare preoperative and postoperative PFT parameters. P value less than0.013 was considered significant for multiple comparisons (PFT parameters) after applying Bonferroni correction.

Results

All 150 patients were able to perform PFT in the immediate postoperative period (within 1 h) and were included in the analysis. Fifty patients each received vecuronium, atracurium, and rocuronium for muscle relaxation. An analysis of TOF ratio on arrival to PACU (TOF at baseline) showed that 57% patients (n = 86) had RNMB (TOF less than 0.9), which persisted in 39 patients (26%) at the time of performing PFT.

Comparison of Vecuronium, Atracurium, and Rocuronium Groups

The three groups were well matched with respect to age, sex, weight, height, body mass index, and type of surgery. Various time intervals like the duration of neuromuscular blockade, the reversal to attaining a TOF ratio of 0.9 or more, the reversal to postoperative PFT measurement, and the time of attaining a TOF ratio of 0.9 or more to postoperative PFT measurement were similar among the groups. During the intraoperative period, less number of patients in rocuronium group (30 [60%]) received NMB agent either as top-ups or infusion compared with vecuronium (37 [74%]) and atracurium (45 [90%]) for the maintenance of muscle relaxation (P < 0.002). The mean ± SD values of TOF ratio on arrival to PACU (TOF at baseline) were 0.79 ± 0.17, 0.81 ± 0.16, and 0.85 ± 0.18 in the vecuronium, atracurium, and rocuronium groups, respectively (P < 0.001). At the time of performing PFT, the mean ± SD values of TOF ratio were 0.87 ± 0.14, 0.89 ± 0.12, and 0.90 ± 0.14 in the vecuronium, atracurium, and rocuronium groups, respectively (P < 0.001). An analysis of TOF at baseline showed that the incidence of RNMB was lower in rocuronium group (23 patients, 46%) compared with vecuronium group (33 patients, 66%) and atracurium group (30 patients, 60%) (P = 0.047). At the time PFT was performed, RNMB persisted in 16 patients (32%) in the vecuronium group, 11 patients (22%) in the atracurium group, and 12 patients (24%) in the rocuronium group, and there was no statistically significant difference in the incidence of RNMB among the three groups (table 1).

Table 1.

Comparison of Study Variables among Patients Receiving Vecuronium, Atracurium, and Rocuronium

The preoperative baseline PFTs were similar among the three groups. Baseline PEF values were 430 ± 104, 407 ± 110, and 414 ± 114 l/min and baseline FVC values were 2.66 ± 0.70, 2.69 ± 0.72, and 2.68 ± 0.74 l in the vecuronium, atracurium, and rocuronium groups, respectively. There was a statistically significant reduction in postoperative PEF (187 ± 99, 182 ± 93, and 192 ± 100 l/min) and FVC (1.46 ± 0.63, 1.61 ± 0.78, and 1.65 ± 0.82 l) in the vecuronium, atracurium, and rocuronium groups, respectively, compared with their respective preoperative values (P < 0.001). The reduction in PEF and FVC from preoperative to postoperative measurements was similar when compared across vecuronium, atracurium, and rocuronium groups (table 2).

Table 2.

Comparison of PFT Parameters among Patients Receiving Vecuronium, Atracurium, and Rocuronium

Subgroup Analysis

For further analysis, based on the TOF ratio at PFT, patients from each group (vecuronium, atracurium, and rocuronium) were subdivided into RNMB absent and RNMB present. The demographic data and other study variables were similar both within and across the subgroups except time intervals (reversal to attaining a TOF ratio of 0.9 or more, reversal to postoperative PFT, and a TOF ratio of 0.9 or more to postoperative PFT) within each group between RNMB-absent and RNMB-present patients (see table, Supplemental Digital Content 1, http://links.lww.com/ALN/A885, comparing study variables among vecuronium, atracurium, and rocuronium groups). There was a statistically significant reduction in postoperative PEF and FVC compared with their respective preoperative values in both RNMB-absent and RNMB-present patients in all three groups (P < 0.001). The reduction in postoperative PFT parameters in RNMB-absent and RNMB-present patients were similar within each NMB group, except the postoperative FVC values expressed as “percentage of preoperative” values in vecuronium group (P < 0.001). The reductions in PFT parameters were similar in RNMB-absent patients across the three NMB groups. The differences in the reductions in PFT parameters in RNMB-present patients across the three NMB groups were not statistically significant (table 3; fig. 2).

Table 3.

Comparison of PFT Parameters between RNMB-present (TOF less than 0.9 at PFT) and RNMB-absent Patients within the Groups and RNMB-present (TOF less than 0.9 at PFT) Patients across Vecuronium, Atracurium, and Rocuronium Groups

Fig. 2.

Postoperative reductions in (A) PEF and (B) FVC values as the percentage of preoperative values in patients with (RNMB-present) and without (RNMB-absent) RNMB among patients receiving vecuronium, atracurium, and rocuronium. Within the groups, only the FVC reduction in RNMB-present patients receiving vecuronium was significantly lower compared with RNMB-absent patients. *P < 0.001 compared with the corresponding RNMB-absent patients. Across the groups, the postoperative PEF and FVC reductions among RNMB-absent patients receiving the three NMB agents were similar, and the difference in postoperative PEF and FVC reductions among RNMB-present patients receiving the three NMB agents was not statistically significant. PEF = peak expiratory flow; FVC = forced vital capacity; RNMB = residual neuromuscular blockade.

Fig. 2.

Postoperative reductions in (A) PEF and (B) FVC values as the percentage of preoperative values in patients with (RNMB-present) and without (RNMB-absent) RNMB among patients receiving vecuronium, atracurium, and rocuronium. Within the groups, only the FVC reduction in RNMB-present patients receiving vecuronium was significantly lower compared with RNMB-absent patients. *P < 0.001 compared with the corresponding RNMB-absent patients. Across the groups, the postoperative PEF and FVC reductions among RNMB-absent patients receiving the three NMB agents were similar, and the difference in postoperative PEF and FVC reductions among RNMB-present patients receiving the three NMB agents was not statistically significant. PEF = peak expiratory flow; FVC = forced vital capacity; RNMB = residual neuromuscular blockade.

Comparison of RNMB-absent and RNMB-present Patients: A Secondary Analysis

All 150 patients were pooled and regrouped as RNMB absent and RNMB present, based on the TOF ratio at PFT irrespective of the NMB agent used. At the time of PFT, 39 patients (26%) had TOF less than 0.9 (RNMB present), and 111 patients (74%) had recovered to a TOF ratio of 0.9 or more (RNMB absent). The mean ± SD values of TOF at the time of performing PFT for groups RNMB absent and RNMB present were 0.95 ± 0.04 and 0.71 ± 0.14, respectively (P < 0.001). All the patients except four in the RNMB-absent group performed PFT within first 30 min of arrival to PACU. There was no difference between the groups in age, sex, weight, height, body mass index, type of surgery, and the type of relaxant used. The use of muscle relaxants for maintenance intraoperatively, as top-ups and infusions, did not differ between the groups (table 4).

Table 4.

Comparison of Study Variables between RNMB Absent and RNMB Present (TOF less than 0.9 at PFT)

Among the time intervals noted, there was no difference between the groups in the duration of neuromuscular blockade. After reversal, patients in the RNMB-absent group attained a TOF ratio of 0.9 or more earlier when compared with patients in the RNMB-present group (9 [6–13] min compared with 20 [15–28] min, P < 0.001). Patients in the RNMB-absent group performed postoperative PFTs at 15 (10–25) min after reversal when compared with RNMB-present patients who could do it at 10 (5–15) min after reversal (P less than 0.001). The patients in the RNMB-absent group attained a TOF ratio of 0.9 or more at 2 (0–10) min before they could perform postoperative PFT, compared with patients in the RNMB-present group who attained a TOF ratio of 0.9 or more at 10 (5–10) min after performing postoperative PFT (P < 0.001) (table 4).

The preoperative baseline PFTs were as follows: PEF, 415 ± 111 and 413 ± 102 l/min; FVC, 2.67 ± 0.70 and 2.69 ± 0.78 l in the RNMB-absent and the RNMB-present groups, respectively. The postoperative PFT values were as follows: PEF, 196 ± 101 and 157 ± 79 l/min; FVC, 1.66 ± 0.76 and 1.32 ± 0.65 l in the RNMB-absent and the RNMB-present groups, respectively, which were lower than the preoperative (baseline) values (P < 0.001) (table 5). The absolute values of postoperative PEF (P = 0.030) and FVC (P = 0.014) were lower in the RNMB-present group compared with the RNMB-absent group but were not statistically significant (after Bonferroni correction). The postoperative PFT values as a percentage of baseline were as follows: PEF, 47 ± 18% and 38 ± 17% (P = 0.008); FVC, 62 ± 21% and 49 ± 18% (P = 0.001), in the RNMB-absent and RNMB-present groups, respectively (fig. 3). Postoperative FVC and PEF values expressed as a percentage of baseline were lower in the RNMB-present patients (by 13% and 9% in absolute terms, and 21% and 19% in relative terms, respectively) compared with RNMB-absent patients, and these reductions were statistically significant (after Bonferroni correction). None of the patients in both groups had hypoxia, upper airway obstruction, laryngospasm, or aspiration.

Table 5.

Comparison of PFT Parameters between RNMB Absent and RNMB Present (TOF less than 0.9 at PFT)

Fig. 3.

Postoperative reductions in PEF and FVC values as the percentage of preoperative values in patients with (RNMB-present) and without (RNMB-absent) RNMB. The postoperative PEF and FVC reductions were greater in RNMB-present patients than RNMB-absent patients. *P = 0.008, $P = 0.001. PEF = peak expiratory flow; FVC = forced vital capacity; RNMB = residual neuromuscular blockade. Fig. 3. Postoperative reductions in PEF and FVC values as the percentage of preoperative values in patients with (RNMB-present) and without (RNMB-absent) RNMB. The postoperative PEF and FVC reductions were greater in RNMB-present patients than RNMB-absent patients. *P = 0.008,$P = 0.001. PEF = peak expiratory flow; FVC = forced vital capacity; RNMB = residual neuromuscular blockade.

Discussion

Incidence of RNMB

In our study, patients received three commonly used intermediate-acting NMB agents. In the absence of intraoperative TOF monitoring, the overall incidence of RNMB on arrival to the PACU was 57% (n = 86). In a meta-analysis, Naguib et al.12  found a mean incidence of RNMB of 0.544 (95% CI, 0.36–0.73) in patients who received intermediate-acting NMB agents without intraoperative TOF monitoring. The use of intraoperative neuromuscular monitoring is known to reduce the incidence of RNMB in the PACU.13  Despite intraoperative TOF monitoring, some of the studies have reported a high incidence of RNMB (30–50%),7,14  whereas others have reported a lower incidence (3.5–29%).8,15

When individual NMB agents were considered, the incidence of RNMB on arrival to PACU was lower in patients who received rocuronium (46%) compared with those receiving vecuronium (66%) and atracurium (60%) (P < 0.047). The lower incidence of RNMB found with rocuronium is unlikely to be due to any pharmacological variation or advantage but rather may be because of the way it is used in clinical practice. In our study, the maintenance of muscle relaxation was left to the discretion of the consultant anesthesiologist managing the case. Lesser number of patients received rocuronium as top-ups or infusion for the maintenance of muscle relaxation (60%) compared with atracurium (90%) and vecuronium (74%) (P < 0.002). In an earlier study, Maybauer et al.16  reported a similar incidence of RNMB, which was lower in patients receiving rocuronium (44%) compared with those receiving cisatracurium (57%) (P < 0.05). They attributed this to clinicians compensating for longer duration of action of rocuronium by stopping the infusion earlier.

Effect of Residual Paralysis on PFTs

Our study deals with physiological changes (PFT changes) occurring due to unintended complications (RNMB) after a planned intervention (use of NMB agent). We quantified the changes in FVC and PEF as it would reflect the restrictive type of pulmonary functional defect caused by RNMB.8  We found a statistically significant reduction in the postoperative PFT parameters in comparison with the baseline in the immediate postoperative period, more so in the presence of RNMB. These findings when translated to clinical situations could cause potentially serious respiratory complications.

A difference in the reduction of FVC or PEF of 15% or more was deemed to be considered significant in our study. Except for postoperative FVC reduction that occurred in RNMB-present patients of vecuronium group, other groups did not show such a difference in either FVC or PEF reductions. Also, the differences in FVC and PEF reductions in patients with RNMB across the three NMB agents (the primary outcome studied) were not statistically significant. This may be because the number of RNMB-present patients in each group (vecuronium, 16; atracurium, 11; and rocuronium, 12) may be too less to detect any such difference. In other words, our study may be underpowered to detect differences in pulmonary function reductions caused by RNMB occurring with different NMB agents. Also, the study was performed in a clinical-practice–based setup where the maintenance of muscle relaxation was left to the discretion of the anesthesiologist managing the patient. Each group of patients would have received different effective doses of NMB agents for the maintenance of muscle relaxation although all of them received standardized bolus doses at induction of anesthesia.

Further, we regrouped the patients and classified them as RNMB present and RNMB absent based on the presence or absence of RNMB at PFT irrespective of the NMB agent used. We assumed that RNMB produced by the three intermediate-acting muscle relaxants studied was similar with respect to pulmonary effects. In both the groups, PFT parameters were reduced to 40–60% of their respective preoperative values. Postoperative FVC and PEF values of RNMB-present patients were lower by 13% and 9% in absolute terms and 21% and 19% in relative terms, respectively, compared with RNMB-absent patients (table 5). Because the two groups differed only by the presence or absence of RNMB, the greater reductions in postoperative PFT parameters seen in patients with RNMB could be attributed to residual paralysis.

Eikermann et al.17  in their study on volunteers found statistically significant reduction in PFTs at a TOF ratio of 0.5 compared with baseline (TOF, 1.0). They found that at a TOF ratio of 0.5, FVC and PEF were 89% and 87% of baseline. In our study, postoperative FVC and PEF values in patients with RNMB were 79 and 81%, respectively, of that of the recovered patients. This is comparable with the reductions in PFT values seen in the study by Eikermann et al.17  if the PFT values of recovered patients in our study are equated to the baseline values of their study. In a study by Ali et al.18  on nonanesthetized volunteers, vital capacity and PEF were 91.2–99.5% and 94.5–95% of the baseline values at a TOF ratio of 0.6–0.9. In another study on volunteers, Eikermann et al.8  observed that at a TOF ratio of 0.5, FVC decreased to 78 ± 14% of baseline whereas at a TOF ratio of 0.83, FVC recovered to acceptable levels (94 ± 6% of baseline). Eikermann et al.8  stated that FVC is a sensitive indicator of respiratory muscle function. As respiratory muscle weakness results in ineffective cough and inability to clear secretions from airways, FVC recovery is considered important for preventing pulmonary complications. These volunteer studies show statistically significant reductions in PFT values in the presence of RNMB. Our study demonstrates the same in the immediate postoperative period after general anesthesia in which intermediate-acting NMB agents were used in a clinical situation.

PFT is a voluntary act and cannot be performed without the active participation and willingness of the patient. We had aimed to perform PFT within 30 min after the first assessment of TOF on arrival to PACU, and all patients except four in the RNMB-absent group were able to do so. There was a statistically significant difference in the interval between reversal to performance of PFT postoperatively between the RNMB-present group and the RNMB-absent group (P < 0.001) (table 4). A difference of 5 min may not be sufficient to explain the greater reductions in postoperative PFTs seen in patients who developed RNMB, as pulmonary function is known to be depressed for prolonged periods after general anesthesia.19–21  Many authors have found postoperative PFT reductions from 4 h (forced expiratory volume in the first second by 65% and FVC by 60%)19  to as late as 72 h (forced expiratory volume in the first second by 53–77% and FVC by 51–79%)20,21  after general anesthesia. However, our study may be the first one to compare PFT changes within the first hour of postoperative period.

Limitations

Intraoperative neuromuscular monitoring is known to reduce the incidence of postoperative RNMB,13  which was not performed in our study. Using acceleromyography, Baillard et al.22  found discordance between two TOF ratios measured in isolation at 30-s interval in 24% of awake postoperative patients. In an attempt to overcome this, we repeated the TOF measurements and noted the higher of the two consecutive reproducible values. Despite our effort, the values may not be accurate. In addition, a previous study has shown that corresponding values of TOF ratio was higher when measured by acceleromyography compared with mechanomyography, which is the gold standard in neuromuscular monitoring.23  Because acceleromyography was used in our study, we could be underestimating the incidence of RNMB.

Other than FVC and PEF, maximal inspiratory pressure and maximal expiratory pressure are the other two parameters used to quantify postoperative muscle weakness.11  In our study, maximal inspiratory pressure and maximal expiratory pressure were not monitored. Serial postoperative PFT measurements performed at various time intervals, such as 4 h, 1 day, and 3 days postoperatively, would have helped us to know the course of recovery of PFT values to the preoperative levels. In our study, the preoperative FVC values were low. They were 72–74% of the predicted values. This may be because the nomogram used for calculating predicted FVC values did not have correction for race. This still would not have affected our results because each patient acted as his or her own control as we compared postoperative values with their respective preoperative values. The reduction in postoperative pulmonary function in patients with RNMB was found during a secondary analysis of data. Finally, the assumption we made about the effect of RNMB caused by different NMB agents on pulmonary function being similar needs to be tested by an adequately powered study using standardized equipotent doses of muscle relaxants for maintenance of muscle relaxation.

Summary and Conclusion

In our routine clinical practice setup, we studied 150 patients using three different intermediate-acting NMB agents and found 57% had RNMB on arrival to PACU, which persisted in 26% of patients until the time of performing PFT. The comparison of reductions in PFT parameters caused by RNMB among different NMB agents did not show statistically significant difference. When we regrouped the patients, we found that in patients with RNMB, although clinically not apparent, there was a 21% reduction in FVC and a 19% reduction in PEF in the immediate postoperative period compared with patients who had completely recovered from neuromuscular blockade. In conclusion, RNMB results in statistically significant reductions in FVC and PEF in the immediate postoperative period.

References

1.
Hedenstierna
G
:
Respiratory physiology, Miller’s Anesthesia
, 7th edition. Edited by
Miller
RD
,
Eriksson
LI
,
Fliesher
LA
,
Wiener-Kronish
JP
,
Young
WL
.
,
Churchill Livingstone
,
2010
, pp
361
92
2.
Siafakas
NM
,
Mitrouska
I
,
Bouros
D
,
Georgopoulos
D
:
Surgery and the respiratory muscles.
Thorax
1999
;
117
:
458
65
3.
Baurain
MJ
,
Hoton
F
,
D’Hollander
AA
,
Cantraine
FR
:
Is recovery of neuromuscular transmission complete after the use of neostigmine to antagonize block produced by rocuronium, vecuronium, atracurium and pancuronium?
Br J Anaesth
1996
;
77
:
496
9
4.
Shabana
K
,
Divatia
JV
,
Sareen
R
:
Comparison of residual neuromuscular blockade between two intermediate acting non-depolarizing neuromuscular blocking agents- rocuronium and vecuronium.
Indian J Anaesth
2006
;
50
:
115
7
5.
Kim
KS
,
Lew
SH
,
Cho
HY
,
Cheong
MA
:
Residual paralysis induced by either vecuronium or rocuronium after reversal with pyridostigmine.
Anesth Analg
2002
;
95
:
1656
60
6.
Murphy
GS
,
Szokol
JW
,
Marymont
JH
,
Greenberg
SB
,
Avram
MJ
,
Vender
JS
,
Nisman
M
:
Intraoperative acceleromyographic monitoring reduces the risk of residual neuromuscular blockade and adverse respiratory events in the postanesthesia care unit.
Anesthesiology
2008
;
109
:
389
98
7.
Murphy
GS
,
Szokol
JW
,
Marymont
JH
,
Greenberg
SB
,
Avram
MJ
,
Vender
JS
:
Residual neuromuscular blockade and critical respiratory events in the postanesthesia care unit.
Anesth Analg
2008
;
107
:
130
7
8.
Eikermann
M
,
Groeben
H
,
Hüsing
J
,
Peters
J
:
Accelerometry of adductor pollicis muscle predicts recovery of respiratory function from neuromuscular blockade.
Anesthesiology
2003
;
98
:
1333
7
9.
Eikermann
M
,
Vogt
FM
,
Herbstreit
F
,
Vahid-Dastgerdi
M
,
Zenge
MO
,
Ochterbeck
C
,
de Greiff
A
,
Peters
J
:
The predisposition to inspiratory upper airway collapse during partial neuromuscular blockade.
Am J Respir Crit Care Med
2007
;
175
:
9
15
10.
Pellegrino
R
,
Viegi
G
,
Brusasco
V
,
Crapo
RO
,
Burgos
F
,
Casaburi
R
,
Coates
A
,
van der Grinten
CP
,
Gustafsson
P
,
Hankinson
J
,
Jensen
R
,
Johnson
DC
,
MacIntyre
N
,
McKay
R
,
Miller
MR
,
Navajas
D
,
Pedersen
OF
,
Wanger
J
:
Interpretative strategies for lung function tests.
Eur Respir J
2005
;
26
:
948
68
11.
Sharma
GD
:
Pulmonary function testing in neuromuscular disorders.
Pediatrics
2009
;
123 Suppl 4
:
S219
21
12.
Naguib
M
,
Kopman
AF
,
Ensor
JE
:
Neuromuscular monitoring and postoperative residual curarisation: A meta-analysis.
Br J Anaesth
2007
;
98
:
302
16
13.
Murphy
GS
,
Szokol
JW
,
Avram
MJ
,
Greenberg
SB
,
Marymont
JH
,
Vender
JS
,
Gray
J
,
Landry
E
,
Gupta
DK
:
Intraoperative acceleromyography monitoring reduces symptoms of muscle weakness and improves quality of recovery in the early postoperative period.
Anesthesiology
2011
;
115
:
946
54
14.
Kopman
AF
,
Zank
LM
,
Ng
J
,
Neuman
GG
:
Antagonism of cisatracurium and rocuronium block at a tactile train-of-four count of 2: Should quantitative assessment of neuromuscular function be mandatory?
Anesth Analg
2004
;
98
:
102
6
15.
Baillard
C
,
Gehan
G
,
Reboul-Marty
J
,
Larmignat
P
,
Samama
CM
,
Cupa
M
:
Residual curarization in the recovery room after vecuronium.
Br J Anaesth
2000
;
84
:
394
5
16.
Maybauer
DM
,
Geldner
G
,
Blobner
M
,
Pühringer
F
,
Hofmockel
R
,
Rex
C
,
Wulf
HF
,
Eberhart
L
,
Arndt
C
,
Eikermann
M
:
Incidence and duration of residual paralysis at the end of surgery after multiple administrations of cisatracurium and rocuronium.
Anaesthesia
2007
;
62
:
12
7
17.
Eikermann
M
,
Groeben
H
,
Bünten
B
,
Peters
J
:
Chest
2005
;
127
:
1703
9
18.
Ali
HH
,
Wilson
RS
,
Savarese
JJ
,
Kitz
RJ
:
The effect of tubocurarine on indirectly elicited train-of-four muscle response and respiratory measurements in humans.
Br J Anaesth
1975
;
47
:
570
4
19.
Mahul
P
,
Burgard
G
,
Costes
F
,
Guillot
B
,
Massardier
N
,
el Khouri
Z
,
Cuilleret
J
,
Geyssant
A
,
Auboyer
C
:
[Postoperative respiratory function and cholecystectomy by laparoscopic approach].
Ann Fr Anesth Reanim
1993
;
12
:
273
7
20.
Mimica
Z
,
Biocić
M
,
Bacić
A
,
Banović
I
,
Tocilj
J
,
V
,
Ilić
N
,
Petricević
A
:
Laparoscopic and laparotomic cholecystectomy: A randomized trial comparing postoperative respiratory function.
Respiration
2000
;
67
:
153
8
21.
Karayiannakis
AJ
,
Makri
GG
,
Mantzioka
A
,
Karousos
D
,
Karatzas
G
:
Postoperative pulmonary function after laparoscopic and open cholecystectomy.
Br J Anaesth
1996
;
77
:
448
52
22.
Baillard
C
,
Bourdiau
S
,
Le Toumelin
P
,
Ait Kaci
F
,
Riou
B
,
Cupa
M
,
Samama
CM
:
Assessing residual neuromuscular blockade using acceleromyography can be deceptive in postoperative awake patients.
Anesth Analg
2004
;
98
:
854
7
23.
Claudius
C
,
Skovgaard
LT
,
Viby-Mogensen
J
:
Is the performance of acceleromyography improved with preload and normalization? A comparison with mechanomyography.
Anesthesiology
2009
;
110
:
1261
70