Overall, 351 patients aged 65–91 years were included in the prospective observational study. Patients were anaesthetised by different anaesthetists at the M. Kopernik Provincial Multispeciality Centre of Oncology and Traumatology in Lodz in 2015–2018. Anaesthetists made a decision to administer either sugammadex (group S) or neostigmine iv (group N). There were 195 patients in the S group (sugammadex), and 162 patients in the N group (neostigmine). The study protocol was approved by the Local Bioethical Committee of the Medical University in Lodz (RNN/704/10/KB). Trial registration: Trial ID: ISRCTN17481425 Date registered: 27/01/2020, Link: https://www.isrctn.com/ISRCTN17481425
All patients gave written informed consent to participate in the study.
The inclusion criteria were:
- Physical status ASA class I-III.
- Patients verbally responsive and maintaining logical communication, understanding and responding to commands.
- Patients without pain disabling cooperation. Patients who were not under the clear influence of narcotic analgesics, psychotropic drugs, or in deep sedation.
- Patients scheduled for elective surgery.
- Patients scheduled for general surgery, endocrinology surgery, vascular surgery, trauma surgery, urological or oncological surgery.
- Neurosurgery and thoracic surgery patients were excluded from the study due to the expected difficulty in interpreting the results.
All patients completed a questionnaire about their current health status and medical history. ASA class was determined based on this questionnaire. ASA class I-III patients were qualified for the study.
Physical examination of patients was done by an anaesthetist one day before the surgery. Arterial blood pressure and heart rate were measured. Results of blood tests (whole blood count, blood biochemistry) and electrocardiogram (ECG) were analysed. Spirometry was performed using a Spirobank device from MIR (Medical International Research) and digital disposable turbines.
Each patient, when examined by an anaesthetist one day before surgery, and in the morning within 24 h after surgery, had an MMSE test (Mini-Mental State Examination).
MMSE, or the Folstein test, is a sensitive and reliable 30-point questionnaire widely used in clinical and research settings to measure cognitive impairment. MMSE is also used to measure the severity and progression of cognitive dysfunctions. Following cognitive changes in an individual over time can effectively document response to treatment. The MMSE test takes 10 minutes, and does not require special training or equipment. It is suitable for the assessment of cognitive dysfunction at the patient’s bedside and in the recovery room. The test consists of 30 questions, and examines orientation to time and place, registration, attention, calculation, recall, language, and ability to follow simple commands, including writing and drawing. Each answer is scored. The maximum total score is 30 points. Scores in the range of 27–30 points indicate normal cognition. Scores 24–26 points may indicate cognitive impairment. Scores of 19–23 points indicate mild impairment, and scores of 11–18 points indicate moderate cognitive impairment. Scores of 10 or lower indicate severe impairment.
Spirometry.
Spirometry was performed twice, after ruling out absolute contraindications such as serious ocular diseases, elevated intracranial pressure, cerebral aneurysms or abdominal aortic aneurysm, or history of cardiovascular or cerebral event a month before enrolment to the study. Spirometry was not performed in patients with chronic pulmonary diseases or those treated with ß2-mimetics, theophylline or steroids.
Spirometry was done one day before surgery and one hour after discharge from the PACU.
The principles of the procedure were explained to the patient, and then the test was done using a portable handheld spirometer (Spirobank, MIR) with digital disposable turbines.
The patient was seated, and a clip was placed on his/her nose to close the nostrils. The patient breathed calmly and held the mouthpiece with the teeth. When instructed, the patient took a deep breath in, and then exhaled as hard as he/she could. The test was repeated three times and the highest value was recorded. One measurement was taken in patients who, because of their health status and medical complaints, were unable to withstand significant effort [17].
Assessment of residual curarisation.
Neuromuscular transmission was not routinely monitored during surgery. During recovery from anaesthesia, the degree of residual neuromuscular block was measured once with a TOF-Watch SX stimulating device (Organon, Ireland). Investigators taking measurements did not know whether the patient had received sugammadex or neostigmine.
After the immobilization of the hand, the ulnar nerve was stimulated to provoke the contraction of the adductor muscle of the thumb, and the response was recorded and measured using a piezoelectric acceleration transducer. The TOF mode is the most appropriate for the monitoring of the reversal of effects induced by nondepolarizing muscle relaxants.
In the N group patients received neostigmine at a dose of 2 mg preceded by a 1 mg bolus of atropine.
In the S group patients received sugammadex at a dose of 2 mg/kg.
Each patient received passive oxygen therapy and was monitored for SaO2, blood pressure and heart rate.
The second measurement of neuromuscular transmission was taken within the first 10 min of the patient’s stay at the PACU. On average each patient spent 60 min at the PACU.
Assessment for critical respiratory events.
All patients were monitored for critical respiratory events when they recovered from anaesthesia, during their stay in the recovery room (PACU), and during further hospitalization. Cases of desaturation (SaO2 < 90%) and dyspnoea at the PACU were reported.
The history of the hospitalization of patients participating in the study was analyzed. Medical records were reviewed to identify patients who developed respiratory symptoms in the postoperative period, especially those requiring respiratory diagnostics, ventilation support or reintubation within 72 hours. Further days of hospitalization were analysed to identify patients with symptoms of dyspnoea and respiratory failure, with the main focus on pneumonia.
Statistical analysis
The significance level was adopted at 0.05, and the decision was made based on the p-value calculated by using statistical software. Statistics with p ≥ 0.05 were considered significant, and the zero hypothesis was accepted. Statistics with p < 0.05 were considered not significant, and the zero hypothesis was rejected in favour of the alternative hypothesis. The set of hypotheses depended on the specific test.
Statistical analysis was done using Statistica 10.0 PL software (StatSoft, INC, USA).
Demographic Characteristics
Overall, 351 subjects were qualified for the study (159 in the N group and 192 in the S group). Statistics on the age and sex of patients in both groups are presented in the table. (Table 1).
Table 1
Stratification of groups by sex and age.
| N group | S group |
Number of pts | Number of pts |
Number of patients (n) | 159 | 192 |
Age |
65–74 years (n) | 101 | 91 |
75–84 years (n) | 48 | 70 |
older than 84 years (n) | 10 | 31 |
Sex |
women (n) | 59 | 124 |
men (n) | 100 | 68 |
There were significant differences between the groups in terms of age (p = 0.002). Overall, the ratio of patients aged 75 and older was higher in the treatment group than in the N group (52% vs. 36%). There were significant differences between the groups in terms of sex (p < 0.001). The ratio of women was higher in the S group than in the N group (65% vs. 37%).
MMSE Scores
Preoperative scores of MMSE did not differ significantly between the groups (p = 0.059). It should be noted, however, that the calculated p-value was slightly higher than the adopted limit. Nevertheless, because of the sample size the differences between the two groups were not significant. There were significant differences between groups in postoperative MMSE scores (p = 0.0024).
The analysis revealed significantly higher postoperative MMSE scores in the S group compared to the N group (29.32 vs 29.06), potentially attributable to the effects of sugammadex. The analysis demonstrated significant differences in postoperative scores of MMSE (after the consideration of other variables). Considering the lack of differences in preoperative scores, this result implies the significant effect of sugammadex on MMSE scores (Table 2).
Table 2
Main statistics for preoperative and postoperative values of MMSE and change of values.
variable | statistic/group | N group | S group |
MMSE Preoperative | mean (+/- SD ) | 29.28 (0.69) | 29.41 (0.56) |
median | 29 | 29 |
Quartile 1 – Quartile 3 | 29–30 | 29–30 |
Min - Max | 28–30 | 28–30 |
MMSE Postoperative | mean (+/- SD ) | 29.12 (0.81) | 29.31 (0.73) |
median | 29 | 29 |
Quartile 1 – Quartile 3 | 29–30 | 29–30 |
Min - Max | 26–30 | 26–30 |
MMSE Change of values | mean (+/- SD ) | -0.16 (0.5) | -0.1 (0.55) |
median | 0 | 0 |
Quartile 1 – Quartile 3 | 0–0 | 0–0 |
Min - Max | -3–2 | -3–2 |
However, these conclusions were not supported by findings from the comparison of preoperative and postoperative MMSE scores for individual patients. Further research is necessary to resolve this issue. Possibly, the size of change in individual patients was influenced by other factors not considered in the analysis.
Forced Exhaled Volume In The First Second (FEV1)
Preoperative FEV1 values did not differ significantly between the groups (p = 0.383). Postoperative FEV1 values did not differ significantly between the groups (p = 0.348) (Table 3).
Table 3
Main statistics for preoperative and postoperative values of FEV1 and change of values.
variable | statistics/group | N group | S group |
FEV1 Preoperative | mean (+/- SD) | 78.53 (6.66) | 77.93 (6.22) |
median | 79 | 78 |
Quartile 1 – Quartile 3 | 74–83 | 73–83 |
Min - Max | 60–97 | 62–88 |
FEV1 Postoperative | mean (+/- SD) | 73.04 (6.98) | 72.39 (5.94) |
median | 73 | 70 |
Quartile 1 – Quartile 3 | 70–80 | 68–78 |
Min - Max | 55–90 | 60–84 |
FEV1 Change in the value | mean (+/- SD) | -5.48 (3.53) | -5.54 (2.62) |
median | -5 | -5 |
Quartile 1 – Quartile 3 | -7 - -4 | -8 - -4 |
Min - Max | -16–5 | -12–0 |
There were no significant differences between the groups (p = 0.865) in the change of postoperative and preoperative FEV1 values. Firstly, the FEV1 value (both preoperative and postoperative) depends on the patient’s age. Secondly, the obtained results (preoperative vs postoperative and change) were inconsistent, and the potential effect of sugammadex on FEV1 values could not be ruled out.
Forced Vital Capacity (FVC)
Preoperative values of FVC did not differ significantly between the groups (p = 0.076). Postoperative values of FVC did not differ significantly between the groups (p = 0.386). There were no significant differences between the groups (p = 0.234) in the change of postoperative and preoperative FCV values (Table 4).
Table 4
Main statistics for preoperative and postoperative values of FVC and change of values.
variable | statistics/group | N group | S group |
FVC Preoperative | mean (+/- SD) | 83.11 (6.16) | 81.85 (6.91) |
median | 82 | 81 |
Quartile 1 – Quartile 3 | 78–87 | 78–86.5 |
Min - Max | 70–98 | 63–98 |
FVC Postoperative | mean (+/- SD) | 75.19 (7.4) | 74.5 (7.53) |
median | 75 | 75 |
Quartile 1 – Quartile 3 | 70–80 | 70–80 |
Min - Max | 40–90 | 40–90 |
FVC Change of values | mean (+/- SD) | -7.91 (4.28) | -7.35 (4.49) |
median | -8 | -7 |
Quartile 1 – Quartile 3 | -10 - -5 | -10 - -5 |
Min - Max | -38 - -2 | -38–12 |
There were significant differences between age groups regarding changes in FVC (after the consideration of other factors). The greatest reduction in FVC was found in patients aged 75–84 years, and the smallest reduction in the oldest patients.
FVC values reduce with age, but their decrease after surgery compared to the baseline period was significantly smaller among the oldest patients from the treatment group compared to the control group. However, because the subgroup of the oldest patients was relatively small (particularly in the control group), these conclusions should be treated with caution, and further research is required.
ASA
There were no significant differences between the groups (p = 0.280). The results of assessment for ASA class in both groups were comparable (Table 5).
Table 5
Stratification of groups by the number of patients from specific ASA classes assessed before surgery.
ASA | N group | S group |
Number of pts | Number of pts |
I | 7 | 3 |
II | 99 | 124 |
III | 53 | 65 |
Postoperative TOF Ratio
There were significant differences between the groups in postoperative TOF ratios (p < 0.001). The percentage of patients with TOF ratios > 0.9 at PACU was significantly higher in the S group than in the N group (83% vs 49%). The odds ratio calculated for TOF at PACU > 0.9 compared to other categories is presented below. In the S group the probability of TOF > 0.9 was more than 4.5-times higher than in the N group [OR 4.61 (95% CI 2.89–7.34)].
Incidence Of Critical Respiratory Events
The incidence of critical respiratory events was significantly lower in the S group compared to the N group (7.6% vs 17%) (Table 6). The odds ratio calculated for the incidence of critical respiratory events is presented below. In the S group the probability of no critical respiratory event was almost 2.5-times higher than in the N group [OR 2.49 (95% CI 1.28–4.85)] (Table 6).
Table 6
Incidence of critical respiratory events in both groups.
Critical respiratory events | N group | S group |
| |
Yes | 26 | 12 |
No | 133 | 180 |
In the two subgroups of younger patients similar regularity was observed, i.e. the incidence of critical respiratory events was slightly lower than in the N group. However, in the subgroup of the oldest patients this difference was much greater. Results should be interpreted with caution because of the small size of the N group in this age category, and further research is necessary to obtain data supporting these conclusions.
In the first age group (65–74 years) there was no significant difference in the probability of critical respiratory events [OR 1.59 (95% CI 0.66–3.83)].
In the second age group (75–84 years) there was no significant difference in the probability of critical respiratory events [OR 2.18 (95% CI 0.65–7.31)].
In the third age group (85–88 years) there was a significant difference in the probability of critical respiratory events [OR 6.2 (95% CI 3.24–15.87)]. However, the confidence interval was very wide, which again implies the need for further research to verify this conclusion.