Post-operative residual curarisation (PORC) is a serious problem affecting up to 60% of patients undergoing surgical procedures under general anaesthesia with muscle relaxants [1, 2, 3, 4, 5]. Non-depolarising muscle relaxants block the acetylcholine receptors on the motor end-plate and thus acetylcholine cannot bind to them. They act on post- and pre-synaptic receptors. The postsynaptic receptors are responsible for stimulation (also blocking) of muscular fibres. The role of presynaptic receptors is not so well known; however, their role in muscular tone maintenance is implicated.

Due to the action of agents blocking the neuromuscular conduction, successive groups of muscles are relaxed - the oculomotor muscles, muscles of the face, pharynx, limbs, abdominal integuments and finally the diaphragm and intercostal muscles. Muscle relaxants also affect the acetylcholine receptors in other organs, e.g. the heart, or autonomic nervous system, which explains some adverse effects following their use.

The normal muscle function is restored in reverse order compared to relaxation. To accelerate the reversal of normal neuromuscular conduction after non-depolarising relaxants, acetylcholinesterase inhibitors are used (e.g. neostigmine). If the inhibitor is administered too early, the neuromuscular blockade is not reversed and paradoxically may even be prolonged. It is believed that residual curarisation of muscle relaxants results from their action on presynaptic receptors, which is associated with the inhibition of acetylcholine release to the synaptic space.

Some literature reports suggest that many patients extubated after general anaesthesia, whose muscle relaxation was assessed based on clinical features, showed no optimal values of neuromuscular conduction on acceleromyometry [6, 7, 8, 9, 10]. Neostigmine is often administered too early when the concentration of relaxants is still high. Extubation and discontinuation of lung ventilation in patients with PORC pose a risk of respiratory failure [1]. Moreover, the direct threat is possible regurgitation and aspiration of contents to the airway and lungs due to impaired function of the pharyngeal and oesophageal muscles [2].

The objective of the present study was acceleromyometric assessment of neuromuscular conduction after surgeries under general anaesthesia with non-depolarising benzylisoquinolinic muscle relaxants.

METHODS

The observational study was carried out, which involved ASA I-III patients. The surgical procedures were performed under general combined anaesthesia; relaxation of striated muscles was provided with atracurium or cisatracurium.  General anaesthesias were administered by the team of anaesthesiologists according to their best knowledge and clinical experience. In some patients, neuromuscular blockade was reversed using neostigmine. The efficacy of management was assessed based on clinical symptoms: the unsupported head held for 10 sec, handshake for 5 sec, minute ventilation values and maximum inspiration strength [3].

Examinations were performed in the recovery room setting. Neuromuscular conduction was assessed by the acceleromyometric method using a TOF-Guard apparatus (Organon, Holland). The patient’s palm was fixed, skin electrodes placed on the forearm along the ulnar nerve. The nerve was stimulated by the train-of-four (TOF) impulses. The measurements were carried out twice: on arrival to the recovery room (A) and 45 min after (B).

 The values of TOF ratio (TOFR) were assessed, i.e. the proportion between the value of the first and fourth response to stimulation. During the further stage, the use of neostigmine for neuromuscular blockade reversal was determined based on anaesthesia protocols; two groups were distinguished: I – patients receiving neostigmine and II – patients without neostigmine.

To assess the extent of PORC, two TOFR values were assumed: TOFR<0.7 (clinically relevant PORC) and TOFR 0.7-0.9 (slight residual paresis). TOFR>0.9 reflected the safe range of neuromuscular conduction [2, 4].

Statistical analysis was performed using the Excel 2003 program. Data distribution was assessed using the ?2 test. Analysis of variance was used for individual parameters in the groups. Intergroup comparisons were based on the t test of mean pairs with two samples assuming uneven variances; intragroup data were analysed using the matched-pair t test with two samples for the mean. The level of significance was set at p<0.05.

RESULTS

The study encompassed 100 patients aged 16-80 years. Group I included 49 and group II – 51 individuals. The mean age in group I was 46±15 years and in group II – 49±15 years. In both groups, the percentage of women was comparable (67.3% in group I and 65% in group II). Atracurium was used in 44 group I patients and 45 group II patients. Cisatracurium was administered to 5 patients in group I and 6 in group II.

The mean duration of surgery did not differ significantly in both groups – 92±41 min  in group I and 103±47 min in group II. The total dose of atracurium used was also comparable: 77±30 mg and 72±33 mg, respectively. Moreover, the doses of cisatracurium were similar – 17.6±3.3 mg and 18±4 mg, respectively.

At measurement A the percentage of patients with TOFR values indicating relevant and residual PORC were 26% in group II and 48% in group I; it improved 45 min after the first measurement. There were no significant intergroup differences in percentages of patients with TOFR values indicating PORC (Table 1).

DISCUSSION

The agents blocking the neuromuscular conduction used currently are considered safe. The majority of them are characterized by the intermediate duration of action.

The problem of residual action of relaxants is underestimated by the majority of anaesthetists. Partial reversal of neuromuscular blockade is likely to lead to serious complications, such as hypoventilation, hypoxemia, lack of airway patency or regurgitation with possible aspiration to the airways. It should be stressed that adverse residual action of relaxants may be increased by residual effects of anaesthetics used during anaesthesia and analgesics administered for postoperative pain management (opioids, in particular).

The impaired CNS function decreases the muscular tone, so do relaxants acting on presynaptic receptors. This combined action may result in acute respiratory failure called critical respiratory event (CRE), which is diagnosed based on SpO2<90%, PaCO2>50 mm Hg, f<8 min-1 (in adults) and/or mechanical airway obstruction associated with collapsing of the upper respiratory structures. One of the causes of CRE in patients with PORC is a weakened response of chemoreceptors to decreased PaO2 [8, 10]. A serious problem is low efficacy of pharmacological protection of a patient against critical respiratory events with acetylcholinesterase-blocking agents [11].

Another difficult problem is the assessment of complete restoration of conduction or reversal of the neuromuscular blockade. It should be remembered that the clinically assessed characteristics of muscular strength and disturbances at the molecular level might differ markedly. Even if the 100% motor response to nerve stimulation with a single impulse is observed, up to 70% of postsynaptic receptors and unknown number of presynaptic receptors of neuromuscular plates might be occupied by relaxant molecules. Although it seems that relaxation subsided completely, the restoration of conduction at the molecular level is incomplete, which is likely to lead to complications. Symptoms of PORC may also be induced by the varied percentages of blocked receptors (from 20% to 80%); thus, the conclusion is simple – patients with the 100% response to one-second stimulation may present full symptoms of respiratory failure [12].

Two types of stimulation are used to assess the residual action of relaxants: TOF and double burst stimulation (DBS). Since there are only two responses to DBS (stronger than in TOF), their assessment is slightly easier. Instrumental methods of neuromuscular conduction monitoring using e.g. accelerometry are so accurate and objective that there is no need to use DBS; thus, TOF stimulation (with suitable stimulators) is a good and sufficient method of PORC assessment [12].

Clinical assessment of neuromuscular conduction is based on observations of the muscular strength. In most cases, patients are instructed to lift the head, shake hands, cough, swallow and breathe. It is generally believed that clinical assessment is sufficient and no other objective methods are required; however, the study findings invalidate this thesis [10]. It should be remembered that some clinical tests show extremely low specificity and sensitivity. Lifting and holding the head for 5 sec, lifting and holding the leg for 5 sec, handshake for 5 sec and the resistance test on sticking the tongue are considered the best tests to assess the muscular strength. The clinical tests widely used, such as sticking the tongue, opening of eyes or assessment of expiration by feeling the endotracheal tube air flow on the examiner’s hand are unreliable [10].

It is worth noting that the patient presenting the satisfactory cough reflex with the endotracheal tube in place may still be under the influence of relaxants; after extubation, he is likely to develop difficulties in spontaneous maintenance of the airway. This is related to the sequence of neuromuscular blockage subsidence. The diaphragm is a strong muscle and starts to work earlier than the muscles maintaining the airways patent, e.g. muscles of the pharynx or larynx and endotracheal intubation is an extremely potent stimulus inducing the cough reflex [2].

It is known that higher PORC is observed after relaxants of a long action and administration of agents in multiple doses [13]; moreover, PORC may develop after a single injection [5]. For these reasons, the use of neostigmine is recommended in cases of maintenance doses of agents blocking neuromuscular conduction. Such indications also exist if symptoms of residual muscle relaxation occur. During recovery, neostigmine should not be administered until there are at least 10-20% responses to one-second stimulation or 2-3 responses to TOF [12, 14].

There is some controversy as to the degree of response to neuromuscular stimulation, which may be considered safe for extubation. The degree of responses to one-second stimulation should be at least 75% and TOFR at least 0.7. At present, some experts believe, however, that TOFR criteria should be stricter – 0.9 [10]. There are reports confirming that airway obstruction may occur even at TOFR 0.8 [2].

Our findings demonstrated that 26% of patients leaving the operating room had TOFR<0.7, which could have evidenced residual paresis and posed the risk of respiratory failure. McCaul and co-workers [4], who studied neuromuscular conduction following atracurium in 40 patients undergoing surgical procedures, showed that TOFR=0.7 was observed in 70% of individuals on reversal of neuromuscular blockade and in 65% on extubation. According to Baillard and colleagues [9], TOFR=0.7 was found in 42% of 568 patients on arrival to the recovery room; TOFR<0.7 was observed in 33% of 435 subjects extubated before arrival to the recovery room. Debaene and colleagues [5] administered a single dose of vecuronium, rocuronium or atracurium for endotracheal intubation. No successive doses of relaxants were administered, neuromuscular blockade was not reversed; 2 h after administration, 10% of patients had TOFR=0.7 and 37% - TOFR=0.9. This indicates impaired neuromuscular conduction even after a longer period and with single doses of relaxants.

Routine TOFR monitoring reduces substantially the incidence of residual paresis in patients after anaesthesia. Based on our results, it may be supposed that differences between group I and II most likely resulted from too early administration of neostigmine to reverse the neuromuscular blockade. The time from the last dose of the agent blocking cholinergic receptors was probably too short and the relaxant concentration in neuromuscular synaptic spaces was too high.

Neostigmine, as an acetylcholinesterase inhibitor, does not actively remove agents inhibiting neuromuscular conduction from the cholinergic receptor. It increases acetylocholine in the synaptic space, which thus may compete more effectively for a suitable receptor with the relaxant. At appropriately high concentrations of the relaxant, this transmitter cannot gain advantage. Thus, too early attempts to reverse the block in patients still under the effects of relaxants may lead to PORC [4].

The studies carried out over the period of 9 years showed that in 11% of patients with the neuromuscular blockade reversed, TOFR was <0.9. Our findings reveal that this percentage may even be higher, which confirms the thesis that the administration of agents reversing the neuromuscular blockade does not ensure safety of patients.

It has been 30 years since it was demonstrated that PORC is common in patients receiving long acting relaxants [18]. The successive studies confirm that this complication is equally common after agents with an intermediate duration of action. The current guidelines for prevention of PORC include: avoidance of long acting relaxants, continuous monitoring of the degree of relaxation during anaesthesia using suitable devices, effective reversal of conduction blockade in each case of administration of relaxants, thorough assessment of muscular activity in patients after anaesthesia using clinical features and objective measurement methods. Additionally, it should be kept in mind that even if all mentioned conditions are fulfilled, the risk of development of this complication is not fully eliminated [6, 9]. PORC is not a relevant factor affecting the anaesthesia-related morbidity and mortality; yet, it is recommended to avoid all complications resulting from the use of relaxants.

CONCLUSIONS

1. Postoperative residual curarisation is common.

2. Assessments of neuromuscular conduction using clinical tests do not fully concur with the results obtained using objective methods, e.g. acceleromyometry.

3. Patients with the neostigmine-reversed neuromuscular blockade, show no more efficient neuromuscular conduction.

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REFERENCES

1.Berg H, Roed J, Viby-Mogensen J: Residual neuromuscular block is a risk factor for postoperative pulmonary complications: a prospective, randomised, and blinded study of postoperative pulmonary complications after atracurium, vecuronium and pancuronium. Acta Anaesthesiol Scand 1997; 41: 1095-1103.

2.Eikermann M, Groeben H, Husing J, Peters J: Accelerometry of adductor pollicis muscle predicts recovery of respiratory function from neuromuscular blockade. Anesthesiology 2003; 98: 1333–1337.

3.Viby-Mogensen J: Postoperative residual curarization and evidence-based anaesthesia. Br J  Anaesth 2000; 84: 301-303.

4.McCaul C, Tobin E, Boylan JF, McShane AJ: Atracurium is associated with postoperative residual curarization. Br J  Anaesth 2002; 89: 766-769.

5.Debaene B, Plaud B, Dilly MP, Donati F: Residual paralysis in the PACU after a single intubating dose of nondepolarizing muscle relaxant with an intermediate duration of action. Anesthesiology 2003; 98: 1042–1048.

6.Baillard C, Clec’h C, Catineau J, Salhi F, Gehan G, Cupa M, Samama CM: Postoperative residual neuromuscular block: a survey of management. Br J Anaesth 2005; 95: 622-626.

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10.Kopman P, Yee PS, Neuman GG: Relationship of the train-of-four fade ratio to clinical signs and symptoms of residual paralysis in awake volunteers. Anesthesiology 1997; 86: 765–771.

11.Kirkegaard H: Efficacy of tactile-guided reversal from cisatracurium- induced neuromuscular block. Anesthesiology 2002; 96: 45-50.

12.Crul JF: Srodki zwiotczajace i monitorowanie przewodnictwa nerwowo-miesniowego – pytania i odpowiedzi. -Medica Press, Bielsko Biala 1999.

13.Maybauer DM, Geldner G, Blobner M, Puhringer 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: 12-17.

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: 102-106.

15.Viby-Mogenses J: Residual curarisation in the recovery room. Anesthesiology 1979; 50: 539-541.

16.Gatke MR, Viby-Mogensen J, Rosenstock C, Jensen FS, Skovgaard LT: Postoperative muscle paralysis after rocuronium: less residual block when acceleromyography is used. Acta Anaesthesiol Scand 2002; 46: 207–213.

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Address:

*Tomasz Gaszyński
Katedra Anestezjologii iTerapii UM wLodzi
ul. Kopcinskiego 22, 90-153 Lódz
e-mail: tomgaszyn@hotmail.com

Received: 04.10.2008.
Accepted: 23.01.2009.