Most patients under general anaesthesia are given muscle relaxants to facilitate surgical procedures. It is challenging for anesthesiologists to change their practice of subjective assessment of recovery from neuromuscular blockade [1,2]. The confirmatory method is to stimulate a motor nerve and observe the contraction of muscle supplied by the nerve to see the degree of neuromuscular blockade [3]. Incomplete neuromuscular recovery is associated with adverse outcomes in the early post-operative period, which involves upper airway obstruction leading to hypoxia, post-operative muscle weakness and an unpleasant feeling of breathlessness after regaining consciousness during reversal [4,5]. Conventional reversal of neuromuscular block Cholinesterase inhibitors acts indirectly by inactivating the enzyme acetyl cholinesterase (AChE) in the synaptic cleft of the neuromuscular junction (NMJ). Acetylch oline concentration increase dramatically, competing with NMBA molecules at the postsynaptic nicotinic receptors [6]. Neostigmine 0.04–0.07 mg kg−1 has an onset of action within 1 min but its peak effect does not occur for 9 min [7] and its duration of action is only  20–30 min [8]. Muscarinic side-effects of anticholinesterases include nausea and vomiting, bradycardia and prolongation of the QT interval of the electrocardiograph (ECG) [9], bronchoconstriction,[10] stimulation of salivary glands, miosis and increased intestinal tone.

Residual paralysis increases the risk of passive regurgitation of gastric contents because of pharyngeal [11] and laryngeal muscle dysfunction, in spite of adequate diaphragm recovery. There is also evidence that non-depolarizing NMBA interfere with hypoxic ventilatory control [12,13].

After approval from Institutional Ethical Committee, 120 patients were included in the prospective, observational study from January 2020 to June 2020 in the Department of Anaesthesiology at Sir Sunder Lal Hospital. Patients of ASA grade 1 and 2, aged 20-60 years and those who gave written informed consent were included in the study. Patients with allergy to the drugs used in the study, anticipated difficult airway, cardiac comorbidities, respiratory illness, neurological problems, myopathies and obesity were excluded from the study.

Group I patients were administered the reversal agents (a fixed dose combination of 0.5 mg neostigmine and 0.1 mg of glycopyrrolate per milliliter) when TOF value is between 0.4- 0.6. Group II patients were administered the reversal agents when they achieved 10% - 20% of the preoperative tidal volume. Group III patients were administered the reversal agents when they achieved 20-30 % of the preoperative original tidal volume. After extubation in each group the following clinical tests will be performed in the postanesthetic care unit (PACU) to rule out any signs of postoperative paralysis.

1. Visual disturbance
2. Facial weakness
3. Weakness of oral and pharyngeal muscles
4. Sustained head lift for more than 5 seconds
5. Sustained leg lift for more than 5 seconds
6. Grip strength for 5 seconds

The data was entered in MS excel sheet and analysis was done using Statistical Package for Social Sciences (SPSS) version 16. Categorical variables were presented in number and percentage (%) and continuous variables were presented as mean ± standard deviation and median. Quantitative variables were compared using unpaired student t-test Test, chi-square test (when the data sets were not normally distributed) among the three groups. Qualitative variables were correlated using One-way Anova. p value of <0.05 was considered statistically significant.

The demographic data (age, sex, weight) were comparable in the three groups without any significant difference (Table 1).

Primary objective

 The mean time to extubate the trachea was almost equal in Group I and Group III (5.40 ± 2.30 min vs 5.47 ± 2.29 min) which was significantly less than in Group II (9.09 ± 3.01 min) with p-value <0.001 (Table 1).

Secondary objective

Incidence of postoperative residual paralysis was compared among groups which was

statistically significant (p value <0.05). Incidence of residual paralysis is 10% in Group

I and group III where as 30% in group II (Table 2).

Table 1: Demographic parameters and mean time required for Extubation.

Table 2: Comparison of sign of residual paralysis.

Despite introduction of neuromuscular monitoring in operating theatres it is still unavailable in different part of world especially in peripheral setting. In qualitative monitoring of neuromuscular blockade during intra operative and postoperative period there is dilemma about when to give the reversal agents after completion of surgery so that there will be less hemodynamic changes during extubation and there will be less incidence of residual paralysis. Reversal strategy without TOF monitoring was not equivalent to reversal strategy using TOF monitoring supporting latest consensus regarding the use of perioperative TOF monitoring tools [14]. In a study by Shilpi Goyal et al mentioned “With objective neuromuscular monitoring, we can ensure complete recovery from the neuromuscular blockade while avoiding the use of anticholinesterases” [15]. However, Murphy et al in an editorial review mentioned that “The hazards of postoperative residual neuromuscular block are well documented; reversal of neuromuscular blocking agents should be routine” [4].

A study comparing the two strategies similar to our study showed almost the same incidence of paralysis residual with our results (10% in control group with TOF) and group III (where reversal was given at 20-30 % of TV) versus 30 % in clinical group II (where reversal was given at 10-20% of TV). Till now no study has specified when to give reversal whereas in our study we have quantified when to to give neostigmine in control group and clinical groups as suggested by Kopman et al [18].

Studies which are done with or without TOF monitoring, most of the study has given reversal when TOF count (0 to 0.9) by Murphy et al [4], or with minimal spontaneous breathing (Nemes et al [17], Wardhana A et al [16]) and measured TOF value in PACU or after extubation showing signs of residual paralysis and they have given a fixed dose to every patient irrespective of recovery status, TOF value, TOF count and spontaneous efforts. Where as in our study we have given neostigmine 0.02mg/kg when in group I when TOF value lies between (0.4-0.9) or there is sign of spontaneous breathing i.e. fixed tidal volume range which indicating return of diaphragmatic activity and patient efforts as suggested by Miller et al [8].

So mean extubation time after neostigmine administration is 5.40±2.3 mins in Control group (group I), 5.47±2.29 mins in group III but 9.09±3.01 mins in group II with p <0.001 across three groups where p value (p<0.001) across the groups was significant. Another study which used neostigmine without accordance to depth of blockade (50 μg/kg IV for every patient) and shorter reversal‐extubation time of 9 min with signs of residual paralysis incidence rate (15.4%) with a TOF ratio <0.70 where as in our study it was 10% in group 1 and 3 with mean extubation time of 5 mins [16].

In our study we compared the changes in preoperative and post extubation vitals (heart rate, respiratory rate, systolic & diastolic blood pressure, mean arterial pressure) and the p value across each group for each parameter is significant (p<0.001). Although in group II where we have given reversal at 10%-20% of tidal volume has developed tachycardia in 60 percent cases probably due to awareness and presence of residual paralysis which is around in 30 percent cases of group II (which is 10% in group I &III).

We concluded that when we reversal was given in Group III with 20-30% of tidal volume there is less incidence of post operative residual paralysis with stable postoperative vitals which was as equivalent as reversal given at train-of-four value (0.4-0.6) in Group I, as it is recommended practice of anesthesia care. So, in peripheral setting where train of four monitoring is not available this tidal volume criteria might helpful for safe practice and safe recovery of patients from general anesthesia.

Limitations

Our study is based on objective monitoring, not a qualitative monitoring which is a standard while neuromuscular monitoring. The age group is limited to 20- 60 years, so neuromuscular blockade profile in lesser age group population and greater age group population cannot be evaluated. Moreover, our sample size is small. Studies with larger sample sizes and long duration of follow up were needed to validate the results our study. The study population belongs to ASA physical status classification I and II only, so further studies needed to evaluate the neuromuscular monitoring profile among ASA status worse than II. The study population does not have weight more than 100 kg, the neuromuscular blockade profile in extremely obese patient cannot be evaluated.

Funding: nil

Conflict of interest: None declared

Ethical approval: The study was approved by Institutional Ethical Committee. 

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