Edinburgh Paper 2

Veterinary Anaesthesia and Analgesia, 2009, 36, 246–254

doi:10.1111/j.1467-2995.2009.00457.x

RESEARCH PAPER

The post-tetanic count during vecuronium-induced neuromuscular blockade in halothane-anaesthetized dogs Farshid Sarrafzadeh-Rezaei*

DVM, DVSc

& R Eddie Clutton 

BVSc, MRCVS, DVA, Diplomate ECVAA, MRCA

*Department of Clinical Sciences, College of Veterinary Medicine, University of Urmia, Urmia, Western Azerbaijan, IRAN  Department of Veterinary Clinical Sciences, Royal (Dick) School of Veterinary Studies, Easter Bush, Roslin, Midlothian, UK

Correspondence: R Eddie Clutton, Department of Veterinary Clinical Sciences, Royal (Dick) School of Veterinary Studies, Easter Bush, Roslin, Midlothian, EH25 9RG, UK. E-mail: [email protected]

Abstract Objective To evaluate the post-tetanic count (PTC) for predicting the return of reversible neuromuscular blockade at the n. facialis–m. nasolabialis (nF–mNL) and n. ulnaris–mm. carpi flexorii (nU– mCF) nerve-muscle units (NMUs) during profound vecuronium neuromuscular blockade in halothaneanaesthetized dogs. Study design Randomized, prospective, experimental study. Animals Twenty-five dogs (seven male 18 female) undergoing surgery; mean age: 4.8 years; mean body weight 22 kg. Methods Thirty minutes after acepromazine (0.05 mg kg)1) and morphine (0.5 mg kg)1) pre-medication, anaesthesia was induced with intravenous (IV) thiopental and maintained with halothane, N2O and O2. The lungs were mechanically ventilated and endtidal halothane concentration (FE¢HAL) maintained at 1.04%. Neuromuscular transmission was monitored using the train-of-four count (TOFC) at one nF–mNL and both nU–mCF units. Vecuronium (50 lg kg)1 IV) was injected after 15 minutes constant FE¢HAL. When the first twitch (T1) at both nU–mCF units had disappeared (t = 0) one (randomly allocated) ulnar nerve was stimulated every 5 minutes using PTC; TOF stimulation continued at the other sites. The PTC was plotted against the interval between

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recording time and T1’s reappearance at the other NMUs. Results At t = 0, the mean PTC in the contralateral nU–mCF unit was 18 (range 0–20). Mean PTC was a minimum at t = 5, rising to the maximum (20) at 25 minutes. Six dogs were vecuronium-resistant as monitored by PTC. Excluding data from these revealed a strong negative relationship between ulnar PTC and the time taken for T1’s return at the facial (r = )0.7018; p < 0.00001) and contralateral ulnar (r = )0.8409; p < 0.00001) NMUs. Conclusion and clinical relevance Post-tetanic count monitoring beginning >5 minutes after the TOFC at nU–mCF = 0 provided a reliable estimate of T1’s return at ulnar and facial NMUs. Keywords dogs, halothane, post-tetanic count, vecuronium.

Introduction During profound neuromuscular blockade, supramaximal nerve stimulation using the train-of-four (TOF) or single twitch stimulation patterns fails to evoke muscular contraction and complicates the monitoring of neuromuscular transmission. However, tetanic stimulation augmented acetylcholine release for approximately 90–120 seconds in response to low-frequency stimulation (Bowman et al. 1984) and so ‘twitches’ may be detected in

Post-tetanic count in dogs F Sarrafzadeh-Rezaei and RE Clutton

profoundly relaxed subjects – albeit for a short period – after tetanic nerve stimulation. Viby-Mogensen et al. (1981) capitalized on post-tetanic facilitation to develop the post-tetanic count (PTC) – a stimulation pattern for monitoring intense neuromuscular blockade. The pattern consisted of 5 seconds of 50 Hz tetanic stimulation, a 3-second interval, and then single-twitch stimulation at 1 Hz applied until no further measurable responses were present. The number of post-tetanic responses (twitches) may be counted by palpation or force displacement transduction (Howardy-Hansen et al. 1984). Simultaneously measuring TOF responses in one limb and the PTC in the other, Viby-Mogensen et al. (1981) reported a correlation between the PTC and the time until spontaneous recovery of TOF. Consequently, PTC not only quantifies the depth of intense neuromuscular blockade, but can be used to predict the time elapsing before reversible block, i.e., when the first twitch in TOF (Caldwell et al. 1986; Engbaek et al. 1990) is present. The PTC has not been evaluated in dogs. This is unfortunate because profound neuromuscular blockade is desirable in operative procedures where sudden unexpected movement may be catastrophic, e.g. spinal, intracranial or intra-ocular surgery, or where the operation involves nerve-muscle units (NMUs) resistant to neuromuscular blocking agents. Marked variation in individual sensitivity to muscle relaxants also ensures profound relaxation occurs in a proportion of animals given normal or even low doses. This is more likely when neuromuscular transmission is monitored in sensitive NMUs. Hall et al. (2001) considered the n. ulnaris–mm. carpi flexorii (nU–mCF); unit to be most useful for monitoring neuromuscular blockade in dogs, in part because Cullen et al. (1980) failed to establish normal facial muscle responses in dogs. Recent study indicated the reliability of facial mechanomyography in dogs and revealed the relative sensitivity of the n. facialis–m. nasolabialis (nF–mNL) unit to vecuronium compared with m. ulnaris–mm. carpi flexorii (Sarrafzadeh-Rezaei & Clutton 2009). The objective of the current study was to evaluate the PTC for predicting the return of reversible vecuronium-induced blockade at the nU–mCF and at m. facialis–m. nasolabialis units in halothane-anaesthetized dogs. Materials and methods Neuromuscular blockade was produced with vecuronium (50 lg kg)1) in 25 dogs of various breeds

and either gender presented at the Hospital for Small Animals, University of Edinburgh over a 6-month period for surgery in which neuromuscular blockade was used as part of the anaesthetic technique. The mean [±standard deviation (SD); range] age of animals studied was 4.8 ± 3.1 (0.5–10) years and mean body mass was 22 ± 7.8 (10–39) kg. Five entire males, two castrated males, eight entire females and 10 neutered females were studied. Other characteristics are detailed in Table 1. Animals not in full health (based on medical history, physical, haematological and biochemical examination), extremes of age (<6 months and >10 years), the extremely lean or obese and those receiving medication known to affect neuromuscular transmission were excluded from study. The project was approved by the Institutional Ethical Review Committee. Food was withheld overnight and water removed 1 hour before pre-anaesthetic medication, which was acepromazine (ACP, C-Vet; Grampian Pharmaceutical Ltd, Lancashire, UK) 0.05 mg kg)1 mixed in the same syringe with morphine (Celltech Pharmaceuticals Limited, Berkshire, UK) 0.5 mg kg)1 and administered by intramuscular injection into the lumbar epaxial muscles 30 minutes before induction of anaesthesia. A cannula was placed in the cephalic vein and an injection cap connected. General anaesthesia was induced with intravenous (IV) 2.5% thiopental given to effect. The trachea was intubated with a cuffed endotracheal tube and anaesthesia maintained with halothane delivered from a calibrated vaporizer (Fluotec vaporizer; Cyprane, Keighley, UK) and carried in an O2:N2O (1:2) mixture via an appropriate anaesthetic breathing system (Mapleson A, D, F or circle). Ringer’s lactate solution was infused at 10 mL kg)1 hour)1. For approximately 15 minutes after induction dogs breathed spontaneously, but intermittent positive pressure ventilation was later imposed using a mechanical ventilator (Manley Pulmovent, Model MPP; BOC Medishield, London UK). A paediatric flow restrictor was used in animals weighing <12 kg (Tunstall 1973). Before surgery began, gas flows were set at 200 mL kg)1 minute)1, but these were later adjusted to maintain end-tidal carbon dioxide tensions (PE¢CO2) between 5.0 and 5.8 kPa (38–44 mmHg) (Millennia Model 3500, Vital Signs Monitoring System; In Vivo Research Inc, Orlando, FL, USA). The vaporizer settings were adjusted to maintain FE¢HAL concentrations at 1.2· published MAC values (Eger et al. 1965) i.e., 1.04%.

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Age (years) Body mass (kg) Gender Male Neutered M Female Neutered F Breeds Labrador retriever Golden retriever Labrador cross Springer spaniel Cross bred Airedale terrier English Bull terrier German Shepherd Rough collie Rottweiler Standard poodle Vizsla Yorkshire terrier cross Operations CCL repair

‘Nonresistant’ (n = 19)

‘Resistant’ (n = 6)

4.6 ± 3.0 (0.5–10.0) 24.8 ± 7.3* (12.0–38.5)

5.7 ± 3.8 (2–10) 15.2 ± 4.0* (10.0–23.0)

5 2 4 8 1 1 3 2 2 2 2 1 1 1 1 1 1 5

Ovariohysterectomy Exploratory laparotomy Femoral fracture fixation Ectopic ureter

4 3 1 1

Castration Femoral fracture fixation Urinary bladder biopsy Colposuspension Total hip replacement

1 1 1 1 1

Table 1 Characteristics of 25 dogs receiving vecuronium whilst anaesthetized with halothane. Animals were divided into ‘nonresistant’ and ‘resistant’ groups based on responses to the post-tetanic count (PTC)

0 0 4 2 Border collie Cavalier King Charles Spaniel Collie Jack Russell Terrier Lurcher Staffordshire Bull terrier

1 1

Ovariohysterectomy and umbilical herniorrhaphy

1

Ovariohysterectomy and mammary gland tumour

1

Ovariohysterectomy CCL repair Anal sacculectomy Patella luxation

1 1 1 1

1 1 1 1

Data presented as mean ± standard deviation; [range]. The mean body masses between groups were significantly (p < 0.005)* different. CCL, cranial cruciate ligament.

Neuromuscular blockade was monitored initially using the TOF stimulation pattern applied every 12 seconds (83.3 mHz) to both n. facialis and the left and right ulnar nerves. Three programmed peripheral nerve stimulators were used: Bard stimulators (Bard Biomedical, Buffalo, NY, USA) on the facial, and on one ulnar nerve, while a Microstim DB (Microstim DB; Viamed, Keighley, West Yorkshire, UK) was used on the other n. ulnaris. All devices delivered four supramaximal (>60 mA) stimuli each of 0.3 ms duration applied at 2 Hz 248

using transcutaneous stainless steel electrodes passed over each nerve. The Microstim DB, which was used to deliver the PTC, delivered 20 impulses at 1 Hz after 5 seconds of tetanic (50 Hz) stimulation and a 3 second interval. The ulnar nerve was stimulated on the medial surface of the humeroradial joint at the level of the olecranon. The dorsal buccal branch of the facial nerve was stimulated using two electrodes 0.5–1.0 cm apart at the fourth upper premolar tooth. Electrode position was adjusted to ensure maximum responses. In all cases,

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the cathode was positioned distally. The number and strength of evoked responses (twitches) in the carpal flexor muscles were detected by palpation (Lee & Katz 1980) and by observation to determine the train-of-four count (TOFC). Responses in the nasolabial muscles were detected by palpating the retraction of the lateral nasal fold. The brachium and antebrachium of the monitored limbs were lightly wrapped in ‘bubble wrap’ and aluminium foil in an attempt to prevent muscle cooling although neither muscle nor skin temperature were recorded. Neuromuscular blockade was produced with vecuronium (Norcuron; Organon Laboratories Ltd., Cambridge, UK) 50 lg kg)1 injected IV into the injection port of the venous catheter 50– 60 minutes after inhalation anaesthesia was begun, after FE¢HAL had been stable for at least 15 minutes and after 15 trains had been delivered. Injection was completed in <1 second during, which fluids were infused at the greatest rate possible under gravity. The time to disappearance of T4 (latent onset) and T1 (manifest onset) at both facial and ulnar sites were recorded. Once profound block (TOFC = 0) was present in both nU–mCF units (t = 0) the nerve stimulation pattern was changed to PTC in one (randomly assigned) limb and was monitored at 5 minute intervals thereafter. TOF stimulation was continued at 83.3 mHz in the contralateral limb and the nF–mNL unit until the TOFC was 4 in both. Animals were defined as being resistant to the vecuronium if the PTC either never achieved a zero value, or returned to ‡15 within 5 minutes of having done so, despite having a complete loss of the TOFC. Vital signs were monitored throughout anaesthesia, the heart and lung sounds were auscultated with an oesophageal stethoscope and the electrocardiogram was displayed continuously. Oscillotonometry (Dinamap, Critikon, Model 1846SX, Tampa, FL, USA) was used to monitor arterial blood pressure with the cuff positioned on the pelvic limb. All dogs received 0.2 mg kg)1 meloxicam IV (Metacam; Boehringer Ingelheim, Bracknell, Berkshire, UK) before surgery began. Mean arterial blood pressure was maintained >60 mmHg by increasing fluid infusion rate and, or by infusing dobutamine. A thermistor (Edale GC203 Digital Thermometer, Longstanton, Cambridge, UK) was positioned in the oesophagus at heart level and the temperature maintained at approximately 37 C [98.6 F] using a heated table, insulation and a high ambient temperature. The dogs were allowed to recover

spontaneously from neuromuscular blockade. Mechanical lung ventilation was discontinued once all four twitches had returned at the nF–mNL unit, although periodic lung inflation was imposed until spontaneous breathing was judged to be adequate on the basis of: a eupnoeic breathing pattern with normal respiratory rate; pink mucous membranes; SPO2 values >90% PE¢CO2 values between 5.3 and 6.0 kPa (40 and 45 mmHg). Statistics The PTC at each recording was plotted against the interval (in minutes) between the time at recording and the reappearance of T1 at the other nU–mCF and the nF–uNL unit. An exponential regression line was tested (STATISTICA version 6; StatSoft, Ltd, Bedford, UK) on the assumption that drug washout from the neuromuscular junction followed a negative exponential curve. The Mann–Whitney U-test was used to compare differences between age, body mass, the onset of blockade and the return of T1 at the face and ulnar nerve in two, subsequently identified groups of subjects. Yates chi-square test was used to compare the gender distribution between these groups. Data are expressed as mean ± SD. A p value £0.05 was considered to indicate statistical significance. Results On the basis of their response to PTC stimulation six dogs appeared to be relatively resistant to vecuronium. These were not distinguishable from nonresistant dogs in terms of age, gender distribution, breed or operation although they had a significantly lower (p < 0.005) body mass than nonresistant animals (Table 1). After vecuronium injection, the latent and manifest onset times at the nF–mNL unit, were 76 ± 17 seconds (48–120) and 94 ± 21 (48–132) seconds respectively. Corresponding values at the nU–mCF unit were 97 ± 21 seconds (48–144) and 118 ± 24 (48–168) seconds. The facial unit was more sensitive to vecuronium than the nU–mCF group at the onset of blockade: in 21 dogs, the facial T1 disappeared 31 ± 19 (12–72) seconds before T1 at the nU–mCF unit, while in four dogs, T1 disappeared at both the facial and ulnar units within 12 seconds of each other. The loss of T1 at one nU–mCF unit (when t = 0) corresponded to a range of values for the PTC in the

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contralateral unit: in 20 dogs at this time, PTC was 20, two had PTCs of 19, in one animal it was 17 and in the remaining two there were no evoked responses detected. In all dogs, PTCs were a minima at t = 5 minutes, but increased after this so that the maximum possible value of 20 was counted in 19 dogs at t = 20 and was present in all 25 dogs when t = 25 minutes (Fig. 1). There was considerable variation in the PTC count at each recording interval. Whilst T1 at the nU–mCF unit was eliminated in all cases, PTC monitoring revealed that six dogs were relatively resistant to vecuronium. In these, the PTC either never achieved a zero value, (n = 4) or was restored to a high value (15 or more) within 5 minutes of having done so (Fig. 1). There were no differences in latent and manifest onset times at both NMUs in the six dogs proving PTC-

resistant, and those that were not (Table 2). However, the time T1 returned to the nU–mCF unit was significantly (p < 0.02) briefer in resistant animals. Plotting all data points revealed a weak inverse relationship between PTC and the interval between recording time and T1’s reappearance at the contralateral nU–mCF unit and the facial muscle. Wide variation resulted from the high number of cases in which PTC = 20 at t = 0 and data from the six ‘resistant’ animals. However, when data from these and the t = 0 recording interval were excluded, the x-y plots congregated along an exponential regression line for both ulnar (Fig. 2a) and facial units (Fig. 2b). The gradient of the regression line in Fig. 2a links PTC with time T1 returns and is given by: time (minutes) to nU–mCF T1 = 11.945)0.0918 · PTC; (r = )0.8409; p < 0.00001). An exponential line

Figure 1 Dot diagram showing the post-tetanic count taken at 5 minute intervals at the n. ulnaris–mm. carpi flexorii unit after the train-of-four count = 0 at the contralateral nervemuscle unit in 19 ‘normal’ (s) and six vecuronium-resistant dogs ( ) anaesthetized with halothane. The resistant cases showing a PTC of 0 at 5 and 10 minutes are different animals.

•

Table 2 Responses of the n. facialis–m. nasolabialis and the n. ulnaris–mm. carpi flexorii nerve-muscle units to train-of-four nerve stimulation in 25 halothane-anaesthetized dogs after vecuronium (50 lg kg)1). Animals were divided into ‘nonresistant’ and ‘resistant’ groups based on post-tetanic counts after vecuronium

Latent onset (seconds) Manifest onset (seconds) T1 returns (minutes)

Nerve-muscle unit

‘Nonresistant’ (n = 19)

‘Resistant’ (n = 6)

n. n. n. n. n. n.

77 97 92 116 29.6 18.5

72 98 98 124 26.8 14.0

facialis–m. nasolabialis ulnaris–mm. carpi flexorii facialis–m. nasolabialis ulnaris–mm. carpi flexorii s–m. nasolabialis ulnaris–mm. carpi flexorii

± ± ± ± ± ±

19 (48–120) 22 (48–132) 22 (48–132) 27 (48–168) 10.2 (16.2–46.1) 5.7* (10.4–25.6)

± ± ± ± ± ±

8 (60–84) 9 (84–108) 16 (72–120) 10 (108–132) 5.7 (16.2–32.6) 3.3* (10.4–19.8)

Data are presented as mean ± standard deviation; [range]. There were no differences in latent and manifest onset times at either site in the six PTC-resistant dogs. A Mann–Whitney U-test indicated T1 returned at n. ulnaris–mm. carpi flexorii unit significantly (p < 0.02)* more rapidly in resistant animals.

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(a)

(b)

Figure 2 The regression lines linking post-tetanic count (PTC) in the n. ulnaris–mm. carpi flexorii unit with the time (in minutes) T1 returned at (a) the contralateral unit and at (b) the n. facialis–m. nasolabialis unit are described by the expressions T1 return (minutes) at (a) 11.945)0.0918 · PTC (r = )0.8409; p < 0.00001) and at (b) 24.2498)0.044 · PTC (r = )0.7018; p < 0.00001). In (a) negative values for T1 reappearance indicate that T1 returned before the corresponding PTC.

also provided the best fit between PTC with T1 return at nF–mNL (Fig. 2b) with the relationship expressed as time (minutes) to T1 at nF–mNL = 24.2498)0.044 · PTC; (r = )0.7018; p < 0.00001).

Comparing these equations to predict T1’s return at the facial and ulnar units confirmed the suggestion that the nasolabial muscles are more sensitive to vecuronium than the carpal flexor muscles. When

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PTC was 10, the predicted time of T1’s reappearance at the nU–mCF unit was 5 minutes, compared with 16 minutes at the nF-mNL. In most dogs, there was a strong negative relationship between the ulnar PTC and the time taken for T1 to return at the facial and contralateral ulnar NMU, providing readings were not made within 5 minutes of T1 disappearance at the contralateral nU–mCF. Discussion The presence of a PTC when the TOFC was 0 indicated that post-tetanic facilitation occurred at the motor nerve terminals of n. ulnaris in canine, as well as human subjects and that the PTC was a useful indicator of profound neuromuscular blockade in this species. Furthermore, the PTC at the nU–mCF usefully predicted the time when reversible blockade became established at the contralateral nU–mCF and the nF–mNL during recovery from profound vecuronium-induced neuromuscular blockade. In medical studies, the relationship between time to T1 reappearance and the PTC has been established for vecuronium, atracurium and rocuronium (Bonsu et al. 1987; Muchhal et al. 1987; Schultz et al. 2001) and has been described in terms of a nonlinear decrease with the square root of PTC (El-Orbany et al. 2003). The slope of the predicted mean curves in the current study (Figs 2a & b) generated when certain data (vide infra) were excluded were similar to the regression lines derived for other intermediateduration neuromuscular blocking drugs in human patients (Howardy-Hansen et al. 1984; Bonsu et al. 1987; Muchhal et al. 1987; Schultz et al. 2001). Differences in the absolute values obtained probably arose because of different variables, i.e., drugs, doses, experimental conditions and sensitivity of the human n. ulnaris–m. adductor pollicis unit compared with the nU–mCF in dogs. A PTC of 1 at the nU–mCF provided adequate indication of T1’s return at both ulnar and facial units, where the minimum–maximum interval between these events was 6–15 and 13–31 minutes respectively. This confirmed the relative sensitivity of the facial NMUs and indicated that during ophthalmic surgery, for example, a PTC of 1 at the nU–mCF would mean that measureable muscle activity in the face would not return for at least 13 minutes. The high predictive value of PTC monitoring established in the current study depended on excluding data from ‘resistant’ cases, and high 252

PTC values recorded when t = 0. However, this does not detract from the technique’s clinical usefulness for two reasons. First, a high PTC registered within a minute or two of T1’s disappearance could be readily recognized and discounted as an indicator of impending recovery from neuromuscular blockade. Second, ‘resistant’ dogs were readily identified by the persistence of high PTC values, which in turn should warn of potential inaccuracies in the test’s ability to predict T1’s return. The presence of ‘resistant’ dogs in the current study was difficult to explain – as is the mechanism of their resistance. Individual variation in response to neuromuscular blocking agents is well recognized in both humans with d-tubocurarine (Katz 1967) and atracurium (Katz et al. 1982) and in dogs with atracurium (Jones & Clutton 1984; Hall et al. 1985) rocuronium (Alderson et al. 2007) and particularly cis-atracurium (Adams et al. 2001). In other studies involving dogs, the incidence of notable resistance was considerably <6 of 25. One possible reason for the greater incidence reported here is the low dose of vecuronium. However, if under-dosing alone accounted for the failure to lower PTC values in resistant animals, then a slower onset and a more rapid recovery from block would have been expected. The absence of differences in latent and manifest onset times at both NMUs between resistant and nonresistant animals might be explained in terms of a type II error, in which case further study comparing larger groups of ‘resistant’ with ‘nonresistant’ dogs is required. The gender distribution of resistant versus non-resistant animals in this study was not statistically significant although all resistant animals were female. This is unexpected because women are more sensitive to atracurium (Xue et al. 1999) and rocuronium (Mencke et al. 2000) than men. The same is probably true for vecuronium. The apparent volume of distribution of vecuronium in dogs and humans is of the same order as the extra-cellular fluid volume (Booij et al. 1981). This is lower in women than men of similar mass, and theoretically renders the former more sensitive to fixed vecuronium doses. Vecuronium’s volume of distribution at steady state in women and men (164.8 ± 29.3 mL kg)1 versus 201.4 ± 75.8 mL kg)1 respectively) is significantly different (Xue et al. 1998). The mean body mass of resistant dogs was significantly lower than that of the nonresistant cases although previous studies have not indicated that smaller dogs are any more

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resistant to relaxants than large ones (Jones 1985; Jones & Seymour 1985). Furthermore, excessively lean and obese animals were excluded from the current study because obesity altered the human subject’s response to vecuronium (Schwartz et al. 1992). Smaller animals have elevated metabolic rates, which may be expected to accelerate a drug’s disposition and clearance from the body thus conferring the impression of resistance. On the other hand, the body temperature of small dogs is likely to fall more rapidly than in large breeds, which will increase sensitivity to vecuroniuminduced neuromuscular blockade through impaired drug clearance and reduced rate of effect site equilibration (Caldwell et al. 2000). Atypical responders to PTC stimulation have been identified in human subjects (El-Orbany et al. 2003). The value of the PTC to predict the return of reversible block depends on the relaxant (VibyMogensen et al. 1981) and the anaesthetic agents (Saitoh et al. 1998; El-Orbany et al. 2003) used. It also depends on the relaxant dose, at least with rocuronium (Schultz et al. 2001). An examination of any of these factors in dogs would provide avenues for further study. The possibility that low vecuronium doses increased the dispersal of x-y plots linking PTC and predicted T1 return time justifies an examination of higher doses, e.g. 100 lg kg)1, in a larger number of dogs. However, more fundamental work examining the effects of breed, body mass and gender in dogs of similar age on the response to neuromuscular blocking agents seems overdue. In a majority of halothane-anaesthetized dogs, the PTC stimulation pattern applied at the n.ulnaris– m carpi flexorii unit reliably predicted the return of reversible vecuronium-induced neuromuscular blockade at the contralateral NMU and at the n. facialis–m nasolabialis units providing monitoring begins >5 minutes after T1 disappears.

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