Edinburgh Paper 1

Veterinary Anaesthesia and Analgesia, 2009, 36, 55–62

doi:10.1111/j.1467-2995.2008.00432.x

RESEARCH PAPER

The effect of volatile anaesthetics on the relative sensitivity of facial and distal thoracic limb muscles to vecuronium in dogs Farshid Sarrafzadeh-Rezaei*

DVM, PhD

& R Eddie Clutton 

BVSc, MRCVS, DVA, Diplomate ECVAA, MRCA

*Faculty 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 compare n. facialis–m. nasolabialis (nF-mNL) and n. ulnar–mm. carpi flexorii (nU-mCF) sensitivity to vecuronium during halothane or isoflurane anaesthesia. Study design Randomized, prospective, experimental study. Animals Forty-four client-owned dogs (19 male, 25 female) undergoing surgery; mean age: 5.0 years; mean body mass: 24.7 kg. Methods Thirty minutes after acepromazine (0.05 mg kg)1) and morphine (0.5 mg kg)1), anaesthesia was induced with intravenous (IV) thiopental and maintained with either halothane (n = 22) or isoflurane (randomly allocated) in oxygen. The lungs were mechanically ventilated and end-tidal inhaled anaesthetic (FE¢IAA) maintained at 1.2 · MAC values. Neuromuscular transmission at nF-uNL and nU-mCF was monitored using the train of four count. Vecuronium (50 lg kg)1 IV) was injected (t = 0) after 15 trains, 50–60 minutes after inhalational anaesthesia began, when FE¢IAA had been constant for >15 minutes. Times of the disappearance ()) and reappearance (+) of the fourth (T4) and first twitch (T1) were recorded allowing the calculation of: latent (t = 0 to T4)) and manifest onset times (t = 0 to T1)) duration of blockade (T1) to T1+) and drug

effect (T4) to T4+) and recovery time (T1+–T4+). Student’s paired t-test was used to compare simultaneous responses at nF-uNL and nU-mCF. An unpaired t-test was used to compare anaesthetic effects. Results Latent and manifest onset times were significantly (p < 0.05) briefer, blockade and drug effects were significantly longer and recovery from blockade were significantly slower in the nF-mNL unit in both halothane and isoflurane recipients. Profound block duration and drug action were significantly longer and recovery from blockade were significantly slower in halothane recipients at both nerve–muscle units. Conclusion and clinical relevance The nF-mNL was more sensitive than nU-mCF to vecuronium, particularly in halothane-anaesthetized dogs. Keywords dogs, halothane, isoflurane, muscle sensitivity, vecuronium.

Introduction An awareness that different nerve–muscle units (NMUs) respond differently to neuromuscular blocking agents in terms of onset time, intensity and duration of effect is clinically important: monitoring neuromuscular transmission in sensitive, rapidly responding units where effects are 55

Muscle sensitivity to vecuronium in dogs F Sarrafzadeh-Rezaei and RE Clutton

protracted is likely to result in underdosing, causing inadequate surgical conditions when muscles at the operation site are relatively resistant. Conversely, overdose – leading to prolonged neuromuscular blockade – is likely when relaxant administration is based on the responses of resistant, slow-responding and transiently-affected muscles. Differential NMU reactivity to a given muscle relaxant arises from differences in blood flow, muscle sensitivity and monitoring methods. Increased muscle perfusion reduces onset time and maximizes the effects of muscle relaxants whilst shortening their duration of action. Increased muscle sensitivity also shortens drug onset time and intensifies the effect of a given dose, but the duration of and recovery from drug effects are prolonged (Donati 2001). General anaesthetics have complex, agent-dependent effects on muscle blood flow (Vollmar & Habazettl 1993). Furthermore, the effects of a given anaesthetic on muscle perfusion differ between muscles in the same subject (Abdulatif & el-Sanabary 1997). Some anaesthetic agents also affect the sensitivity of muscles to neuromuscular blocking agents (Pollard 1995). It follows that the relative sensitivity of two NMUs depends on the anaesthetic technique. The response of a given NMU to a specified dose of neuromuscular blocking agent also depends on the nerve stimulation pattern applied (Meretoja et al. 1994) and the duration of anaesthesia before muscle relaxant administration (Jalkanen & Meretoja 1997; Plaud et al. 2003). If these are not the same for each NMU then an illusion of differential sensitivity may be created. Cullen et al. (1980) examined evoked mechanical responses of facial (nasal) and thoracic limb muscle during neuromuscular blockade in four, thiopental-anaesthetized dogs. However, they could not report simultaneous responses at each site because of technical problems associated with the recording of nasal muscle activity. In a second study, Cullen & Jones (1980) simultaneously recorded the mechanomyographic effects of succinylcholine, gallamine and pancuronium on nasal and thoracic limb muscles in a number of thiopental-anaesthetized dogs and reported that at any given time, all three agents produced a greater degree of block in the thoracic leg compared with nasal muscles. However, the effects of muscle relaxant over time were not described. 56

This study aimed: 1) to compare the simultaneous responses of the n. facialis–m. nasolabialis and n. ulnaris–mm. carpi flexorii nerve–muscle units to intravenous (IV) vecuronium (50 lg kg)1) and 2) to examine the effects of halothane and isoflurane on this relationship in dogs. Materials and methods The study involved 44 dogs of various breeds and of either gender presented at the Hospital for Small Animals, University of Edinburgh over a six-month period for surgery in which muscle relaxation was required as part of the anaesthetic. Exclusion criteria were: imperfect health (based on medical history, physical, haematological and biochemical examination); extremes of age (<6 months and >10 years); extremes of body condition; and concurrent medication with drugs known to affect neuromuscular transmission. The mean age of animals studied was 5.0 ± 3.1 (standard deviation [SD]) (range: 0.7– 10 years) and mean body mass was 24.7 ± 10.3 (9.6–56.5) kg. See Table 1 for animal details within groups. There were no significant differences between groups in terms of age, body mass and gender distribution. The project was approved by the institutional ethical review committee. Food was withheld overnight and water removed 1 hour before pre-anaesthetic medication with acepromazine (C-Vet, Grampian Pharmaceutical Ltd, Lancashire, UK) 0.05 mg kg)1 and morphine (Celltech Pharmaceuticals Limited, Berkshire, UK) 0.5 mg kg)1 mixed in the same syringe and administered by intramuscular (semimembranosus/semitendinosus group) injection 30 minutes before induction of anaesthesia. A cannula was placed in the cephalic vein and the injection cap connected. General anaesthesia was induced with IV 2.5% thiopental administered to effect. The trachea was intubated with a cuffed endotracheal tube and anaesthesia maintained with either halothane or isoflurane (allocated according to a block randomizing process) was delivered from a calibrated vaporizer (Fluotec or Isotec Mk III vaporizer; Cyprane, Keighley, UK) and was 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 IV, by the cephalic venous catheter, at 10 mL kg)1 hour)1. For approximately 15 minutes after induction of anaesthesia, the dogs breathed spontaneously, but intermittent positive pressure ventilation (IPPV) was later

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Muscle sensitivity to vecuronium in dogs F Sarrafzadeh-Rezaei and RE Clutton

Table 1 Characteristics of forty-four dogs receiving vecuronium whilst anaesthetized with either halothane or isoflurane. Data presented as mean ± standard deviation; [range]. There were no statistically significant differences between groups

Age (years) Body mass (kg) Gender M F Breeds Airedale terrier Border collie Cavalier King Charles spaniel Cross-bred Doberman English bull terrier German shepherd Golden retriever Jack Russell terrier Labrador Lhasa apso Lurcher Newfoundland Rottweiler Rough collie Springer spaniel Standard poodle Staffordshire bull terrier Vizsla Operations Anal sacculectomy Exploratory arthrotomy Castration Cranial cruciate ligament repair Exploratory laparotomy Femoral fracture fixation Ovariohysterectomy Pericardectomy Perineal herniorrhaphy Prosthetic hip implant Patellar luxation Thoracotomy Tumour excison

initiated using a mechanical ventilator (Manley Pulmovent, Model MPP; BOC Medishield, London UK). A paediatric flow restrictor (Tunstall 1973) was used in animals weighing less than 12 kg. Before surgery began, gas flows were set at 200 mL kg)1 but these were later adjusted to maintain the end-tidal carbon dioxide tension (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 end-tidal halothane (FE¢HAL) and isoflurane (FE¢ISO) concentrations at 1.2 · published minimum alveolar concentration (MAC) values, i.e. 1.04% and 1.54% respectively,

Halothane (n = 22)

Isoflurane (n = 22)

5.0 ± 3.0 [0.9–10.0] 22.6 ± 8.1 [10.2–38.5]

5.2 ± 3.2 [0.7–10.0] 26.7 ± 12 [9.6–56.5]

8 14

11 11

1 2 1 5 0 1 1 2 1 1 0 1 0 1 1 2 1 1 0

1 3 0 6 1 0 2 2 0 1 1 1 1 0 0 2 0 0 1

1 0 1 8 3 2 3 0 1 1 1 1 0

1 1 3 5 4 0 3 1 2 0 0 0 2

throughout the study (Eger et al. 1965; Steffey & Howland 1977). Neuromuscular blockade was monitored using the train of four (TOF) stimulation pattern applied at 12 second intervals (83.3 mHz); four supramaximal (>60 mA) stimuli each of 0.3 ms duration were applied at 2 Hz using transcutaneous electrodes passed over the ulnar nerve on the medial surface of the humero-radial joint at the level of the olecranon. The dorsal buccal branch of the facial nerve was similarly stimulated using two stainless steel electrodes passed subcutaneously 0.5–1.0 cm apart in a position approximately overlying the fourth upper pre-molar tooth. The polarity of the stimulating current applied over both nerves

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Muscle sensitivity to vecuronium in dogs F Sarrafzadeh-Rezaei and RE Clutton

was consistent; in all cases, the cathode was distal. Two programmed peripheral nerve stimulators (Bard Biomedical, Buffalo, NY, USA) were used and the number and strength of evoked responses (twitches) in the carpal flexor muscles and m. nasolabialis were detected by palpation (Lee & Katz 1980) and observation to determine the trainof-four count (TOFC). Electrode position was adjusted to ensure maximum responses. The brachium and antebrachium of the monitored limb were lightly enveloped 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 Science Park, Cambridge, UK) 50 lg kg)1 injected IV (t = 0) into the injection port of the venous catheter 50–60 minutes after inhalational anaesthesia was begun, after end-tidal anaesthetic concentrations had been stable for at least 15 minutes and after fifteen trains had been delivered. Injection was completed in <1 second in all animals during which fluids were infused at as rapid a rate as possible under gravity. Vecuronium’s latent onset time, i.e. from t = 0 to the first sign of effect (loss of the fourth ‘twitch’ [T4] in the TOF pattern) and the manifest onset (when T1 disappeared) were recorded. Later, the times at which T4 and T1 were first detected were registered. The interval between loss and return of T4 (T4) to T4+) was calculated and taken to indicate the duration of drug effect, whereas the period of T1 absence (T1) to T1+) was taken to indicate the duration of profound neuromuscular blockade. The interval between the reappearance of T1 and T4 respectively was used as an index of the recovery rate of neuromuscular transmission. Vital signs were monitored throughout anaesthesia, the heart and lung sounds were auscultated with an oesophageal stethoscope and the electrocardiogram was monitored continuously. Oscillotonometry (Dinamap, Model 1846SX; Critikon, Tampa, FL, USA) was used to monitor arterial pressure with the cuff positioned on the thoracic limb not used for monitoring neuromuscular blockade. Particular attention was paid to changes in haemodynamic variables and other signs, e.g. lacrimation, salivation, etc., indicative of inadequate anaesthesia and/or analgesia. Mean arterial blood pressure was maintained at >60 mmHg by increasing fluid infusion rate and/or by infusing dobutamine to effect. A temperature thermistor 58

(Edale GC203 Digital Thermometer; Longstanton, Cambridge, UK) was advanced into the oesophagus to the level of the heart and the oesophageal temperature was 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 both units, although the lungs were inflated periodically until spontaneous breathing was present and judged to be adequate – as indicated by a eupnoeic breathing pattern with normal respiratory rates, pink mucous membranes, SPO2 values >90% and PE¢CO2 values between 5.3 and 6.0 kPa (40 and 45 mmHg). Statistics Data in each group were tested for normality (STATISTICA version 6, StatSoft, Ltd, 21-23 Mill Street, Bedford, UK) using the Shapiro–Wilk’s W test. Normally distributed data sets from either treatment group, i.e. halothane or isoflurane, were compared using an unpaired ‘t’ test. Within each treatment group, the differences in responses at the two nerve–muscle units were compared using a paired Student’s ‘t’ test (parametric) or Wilcoxon’s matched pairs test (nonparametric). Data are expressed as mean ± SD. A p-value £0.05 was considered to indicate statistical significance. Results The mean values for latent onset times were similar in both halothane- and isoflurane-anaesthetized dogs although blockade developed significantly more rapidly (p < 0.01) in the facial muscles (see Table 2). This presaged a similar pattern for the manifest onset time. Vecuronium’s mean duration of effect (T4) to T4+) and of profound effect (T1) to T1+) were significantly longer (p < 0.05) under halothane anaesthesia at both nerve–muscle units, but was always greatest (p < 0.01) in the facial muscles. The mean recovery time from neuromuscular blockade (T1+ to T4+) was greater (p < 0.05) in the facial muscles compared to the n. ulnaris–mm. carpi flexorii unit for both anaesthetics, although recovery was particularly protracted (p < 0.05) in the facial muscles of dogs receiving halothane. The n. facialis–m. nasolabialis unit showed significantly greater sensitivity to vecuronium than

 2009 The Authors. Journal compilation  2009 Association of Veterinary Anaesthetists, 36, 55–62

Muscle sensitivity to vecuronium in dogs F Sarrafzadeh-Rezaei and RE Clutton Table 2 The effect of vecuronium (50 lg kg)1) on the response of n. ulnaris–m. carpi flexorii (nU–mCF) and the n. facialis–m. levator nasolabialis (nF–mLN) units to train-of-four stimulation

Nerve–muscle unit

Variable

Halothane

Isoflurane

nU-mCF nF-mNL nU-mCF nF-mNL nU-mCF nF-mNL nU-mCF nF-mNL nU-mCF nF-mNL

latent onset t = 0 to T4) (seconds) manifest onset t = 0 to T1) (seconds) profound block T1 ) to T1+ (minutes) drug effect T4) to T4+ (minutes) recovery T1+ to T4+ (minutes)

96 75 118 94 17.1 29.2 20.8 33.6 6.1 11.6

101 74 119 92 14.4 23.5 14.9 24.3 4.9 6.2

± ± ± ± ± ± ± ± ± ±

21à [48–144] 15à [48–120] 23à [48–168] 20à [48–132] 4.7*à [10.1–28.4] 6.4*à [16.2–46.1] 6.8*à [10.5–39.5] 8.3*à [21.5–56.8] 1.7  [3.1–9.6] 2.6*  [2.6–11.4]

± ± ± ± ± ± ± ± ± ±

19à [60–132] 18à [48–132] 22à [96–192] 21à [60–132] 2.9*à [10.3–22.6] 7.2*à [12.5–40.7] 3.4*à [10.3–23.1] 7.9*à [13.0–41.1] 1.8  [1.9–9.3] 2.1*  [2.6–10.9]

t = 0, time of vecuronium injection; T4), loss of the fourth ‘twitch’ (T4) in the TOF pattern; T1), loss of the first twitch; T4+, reappearance of T4. Data presented as mean ± standard deviation; [range]. *Significant (p < 0.05) difference between inhalation agents;  significant difference (p < 0.05) between muscles; àsignificant difference (p < 0.01) between muscles.

nU-mCF in all of the five recorded variables, an effect which was greatest in dogs receiving halothane. Discussion The current study revealed the greater sensitivity of the nF-mNL compared with the nU-mCF unit to vecuronium as a shorter onset of neuromuscular block, a longer duration of effect and a slower recovery. It also revealed that vecuronium’s measurable (T4) to T4+) and profound (T1) to T1+) effects were more prolonged at both nerve–muscle units in halothane, rather than isoflurane-anaesthetized animals. Recovery was also slower in halothane recipients, supporting the impression that halothane potentiated neuromuscular blockade to a greater extent than isoflurane. The findings of the current study were unexpected as previous work tends to emphasize the resistance of facial muscle to neuromuscular blocking agents relative to peripheral limb muscles, at least in dogs (Cullen & Jones 1980) and horses (Hildebrand et al. 1989). However, earlier reports may have been misleading, in part because of the imprecise way in which facial muscles have been described. By stimulating the facial nerve and observing responses in the facial muscles in horses, Hildebrand et al. (1989) concluded that the muscles of the face were more resistant to neuromuscular blockade than pelvic limb extensor muscles. This implies that facial muscles respond uniformly to

neuromuscular blockade, which is not the case. In humans, m. orbicularis oculi is more resistant to neuromuscular blocking agents than masseter, which in turn is more resistant than the extraocular muscles (Rupp 1993). Cullen & Jones (1980) reported that neuromuscular blockade was greater in the thoracic leg compared with the nose after succinylcholine, pancuronium and gallamine were administered to four dogs. The conflicting results of this and the current study are not attributable to the methods used for quantifying neuromuscular blockade because the TOFC is directly proportional to T1 depression (Ali et al. 1970). However, technical differences may account for some discrepancies: in a preliminary study, Cullen et al. (1980) stimulated the dorsal buccal branch of the facial nerve and used force–displacement transduction to quantify corresponding movements in the right nostril. They subsequently reported unusual recordings after gallamine and pancuronium had been administered specifically, a dose-dependent twitch depression but without the fade characteristic of nondepolarizing blockade. One explanation is the accidental direct stimulation of the underlying masseter muscle, which would have added noise (with nonfading characteristics) to the diminishing contractions from m. nasolabialis. Other differences between the current and previous work, which may account for the differences observed are: the relaxant drug chosen, the anaesthetic agents used, the duration and nature of nerve

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Muscle sensitivity to vecuronium in dogs F Sarrafzadeh-Rezaei and RE Clutton

stimulation before relaxant administration and the NMU temperature. The extent of the difference in sensitivity between two nerve–muscle units is not constant and depends on the drug involved (Harper 1995). In humans, pancuronium’s duration of effect at m. adductor pollicis is twice that of the diaphragm, with D-tubocurarine, the relative duration of action is 3:1 (Derrington & Hindocha 1990). A disproportionately greater effect of vecuronium (compared with succinylcholine, gallamine or pancuronium) on the facial muscles of dogs would explain the current findings. General anaesthetics alter the response of NMUs to neuromuscular blocking agents through effects on muscle blood flow and by potentiation. Volatile agents increase muscle sensitivity to relaxants to a greater extent than injectable agents in both humans (Pollard 1995) and dogs (Nagahama et al. 2006). Unfortunately, no study appears to have examined the potentiating effects of anaesthetics at more than one nerve–muscle unit at the same time, i.e. there is no evidence for differential potentiation by different drugs at different units. However, Abdulatif & el-Sanabary (1997) reported that thiopental – N2O – isoflurane anaesthesia significantly increased blood flow in m. adductor pollicis whilst having no effect on flow in the orbicularis oculi muscle in human patients. This indicated that the delivery of neuromuscular blocking agents to different muscles depends on the anaesthetic agents used and that the latter may alter the pattern of drug effects. The sensitivity of the nF-mNL unit observed in the current study may have resulted from an increased facial and, or decreased carpal flexor blood flow engendered by the volatile anaesthetics because Cullen & Jones (1980) used thiopental to maintain anaesthesia. Furthermore, they studied responses in thoracic legs immobilized in a padded clamp, which may have affected antebrachial muscle blood flow. The nature and duration of nerve stimulation before relaxant administration are also important. The onset of neuromuscular blockade is more rapid and the degree of block produced greater when the TOF pattern is repeated every 10 rather than every 20 seconds (Meretoja et al. 1994). Similarly, the onset of vecuronium’s action is shorter and its duration is longer when a prolonged period of nerve stimulation precedes the injection of relaxant (McCoy et al. 1995). Cullen & Jones (1980) used repeated TOF stimulation, but did not disclose the period of pre-relaxant stimulation at either nerve– muscle unit examined in their study, so it is possible 60

that a more frequent and/or prolonged stimulation period at the ulnar nerve created spuriously sensitive carpal flexor muscles. In the current study, nerve stimulation began at both sites simultaneously and vecuronium was injected after 15 trains had been delivered, thus preventing variation arising from these factors. In theory, large differences between the temperatures of the nasolabial and the carpal flexor muscles in the current and earlier studies could account for the conflicting results, because a lowering of surface temperature delays the onset, prolongs the duration and delays the recovery from vecuronium-induced blockade in humans (Eriksson et al. 1990). Previous work did not describe the measures taken to minimize the influence of this variable (Cullen & Jones 1980; Cullen et al. 1980). Variation in NMU reactivity to muscle relaxants arose from differences in muscle blood flow and/ or sensitivity (Donati 2001) with increasing blood flow and sensitivity conferring shorter onset times and more intense effects. In the current study, both latent and manifest onset times were more rapid in the nF-mNL than in the nU-mCF unit indicating the former’s greater sensitivity and/or perfusion. The latter may be the result of its proximity to the aorta, compared with distal limb muscles (Donati 1988). However, increased perfusion shortened the duration of relaxation whereas increased sensitivity prolonged block. Therefore, the relative reactivity of the nF-mNL unit in the current study is most easily attributed to a greater sensitivity. In humans, resistance of m. orbicularis oculi compared with m. adductor pollicis (Donati et al. 1990) has been linked with its higher proportion of type 1 fibres (Harper & Wilson 1987) although work in goats indicated resistance is greatest in muscles composed of small fibres with large end-plates relative to fibre size (Ibebunjo et al. 1996). The relevance of this to muscles of the face cannot be established because their morphology, in this context, does not appear to have been studied. Reduced temperature also appears to increase NMU sensitivity to relaxants although its effects on local blood flow may also be important. The greater sensitivity of the nF-mNL compared with the nU-mCF throughout this study and in both halothane and isoflurane recipients could be attributed to a lower muscle temperature at the former unit because lowering surface temperature retarded the onset, extended duration and slowed recovery from vecuronium-induced blockade (Eriksson et al. 1990). In the current study, the

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Muscle sensitivity to vecuronium in dogs F Sarrafzadeh-Rezaei and RE Clutton

nU-mCF unit was insulated and although surface temperatures were not measured, it is possible that they remained higher than those overlying the nF-mNL NMU and conferred the characteristics of resistance. Volatile anaesthetic agents potentiated neuromuscular blocking agents to a greater extent than injectable anaesthetics in humans and dogs. Kastrup et al. (2005) reported that sevoflurane significantly potentiated an atracurium-induced block in dogs compared with a propofol infusion. Similarly, the infusion rate of vecuronium needed to maintain a TOFC of 1 during constant rate infusion (CRI) propofol–fentanyl anaesthesia was double that required during CRI fentanyl–isoflurane or CRI fentanyl–sevoflurane anaesthesia (Nagahama et al. 2006). In humans, the extent of potentiation depended upon the exact volatile agent/muscle relaxant combination. Enflurane and isoflurane potentiated D-tubocurarine and pancuronium block more than halothane, whereas enflurane potentiated vecuronium-induced block more than isoflurane or halothane (Rupp et al. 1984). In the current study, the halothane potentiated, i.e. prolonged, vecuronium’s effects to a greater extent than isoflurane, which was unexpected, as either no difference (Pittet et al. 1990; Woelfel et al. 1991) or the reverse (Rupp et al. 1984) has been reported in humans. Similarly, halothane prolonged recovery from blockade to a greater extent than isoflurane in the current study; this is not the case in humans where no difference (Rupp et al. 1984; Woelfel et al. 1991) or the reverse effect (Pittet et al. 1990) has been reported. The mechanism of potentiation is not clear although in vitro studies indicate that the effect of anaesthetic on muscle blood flow is relatively minor (Pollard 1995). The current study showed that the n. facialis–m. nasolabialis unit is suitable for monitoring vecuronium-induced neuromuscular blockade in anaesthetized dogs because its relative sensitivity reduces the likelihood of overdose. When this is not feasible, e.g. during ophthalmic operations, the greater resistance of the n. ulnaris–mm. carpi flexorii unit must be appreciated. The relatively greater potentiating effects of halothane on vecuronium’s activity indicated that lower doses were required to produce more prolonged blockade, and that repeated low dose injections or infusion may be more suitable when a prolonged effect is required. There is a need to establish the degree of relaxation produced at accessible nerve–muscle units with the

surgical relaxation produced at common operative surgical sites. However, comparing the differential sensitivity of NMUs in animals is rendered almost impossible by the use of nonstandardized stimulating/recording methods applied against a plethora of anaesthetic techniques. The logical consequence of the current study would be to establish whether the relative sensitivity of the facial and distal thoracic limb muscles in dogs is present with other types of muscle relaxants, e.g. rocuronium and doxacurium, and in the presence of modern volatile agents like sevoflurane. Measuring differences in muscle blood flow would be a relatively simple way to elucidate mechanisms of potentiation providing surface and core temperatures were monitored and maintained within physiological, or similar limits. We concluded that the n. facialis–m. nasolabialis unit is more sensitive to vecuronium in dogs than the n. ulnaris –mm. carpi flexorii group, particularly during halothane anaesthesia. References Abdulatif M, el-Sanabary M (1997) Blood flow and mivacurium-induced neuromuscular block at the orbicularis oculi and adductor pollicis muscles. Br J Anaesth 79, 24–28. Ali HH, Utting JE, Gray C (1970) Stimulus frequency in the detection of neuromuscular block in humans. Br J Anaesth 42, 967–978. Cullen LK, Jones RS (1980) Recording of train-of-four evoked muscle responses from the nose and foreleg in the intact dog. Res Vet Sci 29, 277–280. Cullen LK, Jones RS, Snowdon SL (1980) Neuromuscular activity in the intact dog: techniques for recording evoked mechanical responses. Br Vet J 136, 154–159. Derrington MC, Hindocha N (1990) Comparison of neuromuscular block in the diaphragm and hand after administration of tubocurarine, pancuronium and alcuronium. Br J Anaesth 64, 294–299. Donati F (1988) Onset of action of relaxants. Can J Anaesth 35, S52–S58. Donati F (2001) Differential effects of neuromuscular blocking agents. Proceedings of the 7th International Neuromuscular meeting. Belfast, pp. 81 (abstract). Donati F, Meistelman C, Plaud B (1990) Vecuronium neuromuscular blockade at the diaphragm, the orbicularis oculi, and adductor pollicis muscles. Anesthesiology 73, 870–875. Eger EI II, Saidman LJ, Brandstater B (1965) Temperature dependence of halothane and cyclopropane anesthesia in dogs: correlation with some theories of anesthetic action. Anesthesiology 26, 764–770.

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 2009 The Authors. Journal compilation  2009 Association of Veterinary Anaesthetists, 36, 55–62