The incidence of spontaneous movements (myoclonus) in dogs undergoing total intravenous anaesthesia with propofol

doi:10.1111/vaa.12160

Veterinary Anaesthesia and Analgesia

Volume 42, Issue 1, January 2015, Pages 93-98

https://doi.org/10.1111/vaa.12160 Get rights and content

Abstract

Objective

To evaluate the incidence of myoclonus (involuntary movements during anaesthesia, unrelated to inadequate hypnosis or analgesia, and of sufficient severity to require treatment) in dogs anaesthetized with a TIVA of propofol with or without the use of fentanyl.

Study design

Retrospective clinical study.

Animals

Dogs, undergoing general anaesthesia for clinical procedures between January 2012 and January 2013 and subject to TIVA with propofol.

Methods

A retrospective analysis reviewed the medical and anaesthetic records. Animals with existing or potential neurological or neuromuscular pathology in the anamnesis or upon clinical examination and cases with incomplete clinical records were excluded. Myoclonus was considered as involuntary muscle contractions which did not cease following a bolus administration of propofol or fentanyl and, due to their intensity and duration, made continuation of the procedure impracticable without other drug administration. Tremors, paddling or muscle spasms, explicable as insufficient hypnosis or analgesia, and transient excitatory phenomena only present during the awakening phase, were not considered as myoclonus.

Results

Out of a total of 492 dogs undergoing anaesthesia, six mixed breed dogs (1.2%), one male and five females, American Society of Anaesthesiologists (ASA) physical status I, median (range) weight 20.5 (7–37) kg and age 1.5 (1–5) years had myoclonus according to the aforementioned definition. In all subjects, myoclonus appeared within 20 minutes after induction of anaesthesia, and mainly involved the limb muscles. All subjects appeared to be in an adequate plane of anaesthesia before and during myoclonus.

Conclusions and clinical relevance

This study shows that 1.2% of dogs, undergoing TIVA with propofol with or without fentanyl administration, developed myoclonus, which required to be, and were treated successfully pharmacologically. The cause of this phenomenon is yet to be determined.

Introduction

Propofol (2,6-diisopropylphenol) is one of the most widely used injectable anaesthetic agents for the induction and maintenance of general anaesthesia, both in humans and veterinary practice. In humans, a number of cases of spontaneous involuntary excitatory movements, presumably induced by the drug, have been reported. The occurrence of these phenomena has also been reported in dogs (Hall & Chambers 1987; Davies 1991; Robertson et al. 1992). The incidence in dogs of involuntary spontaneous movements during propofol based total intravenous anaesthesia (TIVA) reported by Hall & Chambers (1987) was five cases out of 23 (21.7%). Davies (1991) reported 12 cases of excitatory spontaneous involuntary movements out of 159 dogs (7.5%). In her report propofol had been administered for induction and, in some cases, also for maintenance of anaesthesia, and in most of the cases the involuntary movements occurred upon induction or recovery of anaesthesia. Robertson et al. (1992), in an experimental study, reported spontaneous involuntary movements in six of 13 (46.1%) dogs in which anaesthesia had been induced and maintained with propofol for one hour. In this study, unlike the previous, almost all of the phenomena occurred several minutes after the administration of propofol and then continued for the duration of anaesthesia.

In human medicine many authors have pointed to the difficulty in accepting that a drug with strong evidence of anti-convulsant activity, in certain circumstances, could be pro-convulsant. However, propofol can induce seizure-like phenomena (SLP), excitatory phenomena, and/or disorder of muscle tone during induction and maintenance of, or emergence from anaesthesia in epileptic and non-epileptic patients (San-juan et al. 2010). Reports refer to qualitatively different effects and it is difficult to quantify the incidence of these complications.

The incidence of spontaneous movements in dogs anaesthetized with propofol appears to vary significantly from study to study. However, our impression is that the incidence of such phenomena, in clinical practice, is lower than previously reported. The objective of this retrospective study is to assess the incidence of involuntary spontaneous movements, of such severity as to interfere with the procedure, associated with the use of propofol in healthy anaesthetized dogs undergoing TIVA with propofol, and to define them in relation to the characteristics of their onset.

Section snippets

Materials and methods

A retrospective analysis was performed reviewing the medical and anaesthetic records of all dogs anaesthetized with a TIVA including propofol at the ‘Clinica Veterinaria dell’Adriatico’, Vasto, Italy, or at the Department of Animal Medicine, Production and Health of the University of Padua Italy, in a period between January 2012 and January 2013. In this study, subjects that presented with current, existing or potential (as a side effect of other disease processes) neurological or neuromuscular

Results

The anaesthesia records of 509 dogs subject to various procedures were included in the study. Of these dogs, 17 then were excluded, as they were incomplete. Thus 492 dogs remained in the study. Overall, 202 (41.1%) of dogs were male and 290 (58.9%) female. The mean ± standard deviation age was 29 ± 9 months, and body weight was 16.9 ± 10.5 Kg. The most common breeds represented were mixed breed [122 (24.8%)]. Only 58 of 492 (11.8%) cases included in this study received premedication, and of

Discussion

In this study, the incidence of involuntary movements was 1.2% (one case out of 82), far lower than that previously reported in veterinary literature (Hall & Chambers 1987; Davies 1991; Robertson et al. 1992). Various factors may explain this finding. Our definition of myoclonus may have played an important role. It was deliberately restrictive, in order to consider only those cases that were based on characteristics of onset and lack of response to dosing increase, so that it could (most

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Propofol and the electroencephalogram
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Lidocaine pretreatment for the prevention of propofol-induced transient motor disturbances in children during anesthesia induction: a randomized controlled trial in children undergoing invasive hematologic procedures
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(2006)
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Propofol and spontaneous movements: an electroencephalographic study
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LW Hall et al.
A clinical trial of propofol infusion anaesthesia in dogs
J Small Anim Pract
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The administration of a propofol bolus or an increase in propofol Cp (as per our algorithm) did not result in resolution of the myoclonus. This agrees with Cattai et al. (2015), who stated that true myoclonus is not related to a superficial anaesthetic plane during propofol TIVA, and it is erroneous to increase propofol administration in an attempt to counteract it. In our study, inhalation of isoflurane suppressed myoclonus in all dogs.
To compare a propofol continuous rate infusion (CRI) with a target-controlled infusion (TCI) in dogs.
Randomized prospective double-blinded clinical study.
A total of 38 healthy client-owned dogs.
Dogs premedicated intramuscularly with acepromazine (0.03 mg kg^–1) and an opioid (pethidine 3 mg kg^–1, morphine 0.2 mg kg^–1 or methadone 0.2 mg kg^–1) were allocated to P-CRI group (propofol 4 mg kg^–1 intravenously followed by CRI at 0.2 mg kg^–1 minute^–1), or P-TCI group [propofol predicted plasma concentration (Cp) of 3.5 μg mL^–1 for induction and maintenance of anaesthesia via TCI]. Plane of anaesthesia, heart rate, respiratory rate, invasive blood pressure, oxygen haemoglobin saturation, end-tidal carbon dioxide and body temperature were monitored by an anaesthetist blinded to the group. Numerical data were analysed by unpaired t test or Mann–Whitney U test, one-way analysis of variance and Dunnett’s post hoc test. Categorical data were analysed with Fisher’s exact test. Significance was set for p < 0.005.
Overall, propofol induced a significant incidence of relative hypotension (mean arterial pressure 20% below baseline, 45%), apnoea (71%) and haemoglobin desaturation (65%) at induction of anaesthesia, with a higher incidence of hypotension and apnoea in the P-CRI than P-TCI group (68% versus 21%, p = 0.008; 84% versus 58%, p = 0.0151, respectively). Propofol Cp was significantly higher at intubation in the P-CRI than P-TCI group (4.83 versus 3.5 μg mL^–1, p < 0.0001), but decreased during infusion, while Cp remained steady in the P-TCI group. Total propofol administered was similar between groups.
Both techniques provided a smooth induction of anaesthesia but caused a high incidence of side effects. Titration of anaesthesia with TCI caused fewer fluctuations in Cp and lower risk of hypotension compared with CRI.
Intraoperative effect of low doses of ketamine or dexmedetomidine continuous rate infusions in healthy dogs receiving propofol total intravenous anaesthesia and epidural anaesthesia: A prospective, randomised clinical study
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This increased respiratory depressant effect of ketamine strongly suggests the provision of mechanical ventilation. Myoclonus is a common adverse effect of propofol TIVA (Cattai et al., 2015; Robertson et al., 1992) and we found an overall incidence of forelimb myoclonus (20%). However, these episodes resolved spontaneously without intervention.
The present study aimed to determine the effect of either ketamine or dexmedetomidine constant rate infusion (CRI) on intraoperative propofol anaesthetic requirements during total intravenous anaesthesia (TIVA) in healthy dogs undergoing hindlimbs orthopaedic procedures receiving epidural anaesthesia. In this randomised, blinded clinical study, thirty-nine healthy client-owned dogs were premedicated intramuscularly (dexmedetomidine 4 μg/kg and methadone 0.3 mg/kg). General anaesthesia was induced to effect with propofol administered as intravenous bolus, and maintained with propofol TIVA (18 mg/kg/h), adjusted to meet the suitable clinical anaesthetic depth (indicatively±20%) based on clinical judgement. Lumbosacral epidural anaesthesia was performed using bupivacaine (1 mg/kg) and morphine preservative free (0.1 mg/kg). Dogs randomly received either saline (SP; loading dose 1 mL/kg, CRI 1 mL/kg/h), or ketamine (KP; loading dose 1.5 mg/kg, CRI 1.5 mg/kg/h), or dexmedetomidine (DP; loading dose 1 μg/kg/, CRI 1 μg/kg/h). Physiological variables were recorded intraoperatively at 5-min intervals using standard-of-care monitoring. Recovery quality and duration were recorded. Treatment groups were compared with parametric and non-parametric tests as appropriate, p < 0.05.
Propofol rates and recovery scores were similar between groups. Overall mean and diastolic blood pressures were higher in group DP compared to group KP (12–14 mmHg, p = 0.016 and p = 0.015, respectively). More dogs required mechanical ventilation in group KP (12 dogs) than in either group SP or DP (7 dogs per group, p = 0.037).
Ketamine or dexmedetomidine CRIs, at the studied rates, did not reduce propofol TIVA requirements in dogs undergoing orthopaedic surgery with epidural anaesthesia.
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This reaction has been reported by other studies in dogs. Cattai et al.14 reported six occurrences of muscular reactions among 492 (1.2%) dogs undergoing propofol anesthesia and proposed an antagonistic effect of propofol on glycine receptors at the spinal cord and brainstem as a possible explanation. The authors discussed that many motor centers (red nucleus, vestibular nucleus, reticular formation and cerebellar nucleus) project to those areas and modulate abnormal movement when stimulated.
This study aimed to investigate the effects of a single bolus and continuous rate infusion (CRI) of 1% propofol on cholesterol and triglyceride levels of healthy bitches undergoing elective ovariohysterectomy. 10 healthy bitches undergoing elective ovariohysterectomy had blood samples obtained at baseline (T_B), 15 minutes following premedication with acepromazine and morphine (T_PM), after an intravenous bolus of propofol (induction to anesthesia, T_IND) and following 90 minutes of CRI of propofol started at 0.4 mg kg⁻¹ min⁻¹ and adjusted according to individual requirements (T_CRI). Data were initially tested for normality using the Shapiro-Wilk test, and comparisons were performed using Friedman followed by Dunn post-hoc test. Serum cholesterol levels significantly decreased at T_IND and T_CRI (median [min-max] 201 mg dL⁻¹ [111-234 mg dL⁻¹], and 215 mg dL⁻¹ [111-239 mg dL⁻¹]), respectively, compared with T_B (232 [128-245 mg dL⁻¹]) and T_PM (206 [115-255 mg dL⁻¹]). No differences were found between T_IND and T_CRI. Triglyceride levels increased significantly at T_IND (120 [67-231 mg dL⁻¹]) and T_CRI (229 [73-549 mg dL⁻¹]) compared with T_PM (36 [51-29 mg dL⁻¹]), and T_CRI compared with T_B. In conclusion, 1% propofol lipid emulsion significantly increases serum triglycerides and causes lipemia in healthy dogs at a single bolus or CRI.
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PE values show a slight tendency to be higher at higher target Cp (Fig. 1), which may be related to incomplete mixing at greater rates of drug delivery (Swinhoe et al. 1998). In this study, neither apnoea nor involuntary movements or other anaesthetic-related adverse effects were observed during induction and maintenance of anaesthesia despite having been reported to be possible after propofol administration in dogs (Smith et al. 1993; Cattai et al. 2015). The setting of a maximum rate based on weight to reduce the risk of respiratory depression potentially related to rapid infusions, and the selection of the induction target in accordance with the level of sedation, may have contributed to this result.
To develop a population pharmacokinetic model for propofol target-controlled infusion (TCI) in dogs and to evaluate its performance for use in the clinical setting.
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A group of 40 client-owned dogs undergoing general anaesthesia for magnetic resonance imaging.
Propofol was administered to 26 premedicated dogs and arterial blood samples were collected during the infusion and over 240 minutes after terminating the infusion. Propofol concentrations were measured by high-performance liquid chromatography. A population pharmacokinetic analysis was performed using a nonlinear mixed-effects modelling approach, allowing inter- and intra-individual variability estimation and quantitative evaluation of the influence of the following covariates: weight, body condition score, age, size-related age (Age_size), sex, premedication type, size and contrast agent administration. A final model was obtained using a stepwise approach in which individual covariate effects on each pharmacokinetic variable were incorporated. The performance of the developed TCI model was subsequently evaluated while inducing and maintaining anaesthesia in 14 premedicated dogs and assessed by comparing predicted and measured concentrations at specific time points.
Propofol pharmacokinetics was best described by a three-compartment model. Weight, Age_size, premedication and sex showed significant pharmacokinetic effects. Addition of the significant covariate/variable associations to the final model resulted in a reduction of the objective function value from 285.53 to –22.34. The median values of prediction error and absolute performance error were 3.1% and 28.4%, respectively. Induction targets between 4.0 and 6.5 μg mL^–1 allowed intubation within 5.0 ± 0.9 minutes. Anaesthesia was achieved with targets between 3.0 and 6.5 μg mL^–1. Mean time to extubation was 9.7 ± 2.6 minutes. All dogs recovered smoothly and without complications.
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Citation Excerpt :
The induction and recovery phases were considered smooth in all dogs on all occasions, despite the presence of myoclonus in two dogs in the recovery period. Myoclonus has been reported in association with propofol administration in dogs (Robertson et al. 1992; Ferreira et al. 2015; Reed et al. 2015; Davis et al. 2017) with an incidence of 1.2% (Cattai et al. 2015). All episodes of myoclonus resolved spontaneously within 20 minutes after extubation.
To determine the effect of dexmedetomidine on induction dose and minimum infusion rate of propofol preventing movement (MIR_NM).
Randomized crossover, unmasked, experimental design.
Three male and three female healthy Beagle dogs weighing 10.2 ± 2.8 kg.
Dogs were studied on three occasions at weekly intervals. Premedications were 0.9% saline (treatment P) or dexmedetomidine (1 μg kg⁻¹, treatment PLD; 2 μg kg⁻¹, treatment PHD) intravenously. Anesthesia was induced with propofol (2 mg kg⁻¹ and then 1 mg kg⁻¹ every 15 seconds) until intubation. Anesthesia was maintained for 90 minutes in P with propofol (0.5 mg kg⁻¹ minute⁻¹) and saline, in PLD with propofol (0.35 mg kg⁻¹ minute⁻¹) and dexmedetomidine (1 μg kg⁻¹ hour⁻¹), and in PHD with propofol (0.3 mg kg⁻¹ minute⁻¹) and dexmedetomidine (2 μg kg⁻¹ hour⁻¹). The stimulus (50 V, 50 Hz, 10 ms) was applied to the antebrachium, and propofol infusion was increased or decreased by 0.025 mg kg⁻¹ minute⁻¹ based on a positive or negative response, respectively. Data were analyzed using a mixed-model anova and presented as mean ± standard error.
Propofol induction doses were 8.68 ± 0.57 (P), 6.13 ± 0.67 (PLD) and 4.78 ± 0.39 (PHD) mg kg⁻¹ and differed among treatments (p < 0.05). Propofol MIR_NM values were 0.68 ± 0.13, 0.49 ± 0.16 and 0.26 ± 0.05 mg kg⁻¹ minute⁻¹ for P, PLD and PHD, respectively. Propofol MIR_NM decreased 59% in PHD (p < 0.05). Plasma propofol concentrations were 14.04 ± 2.30 (P), 11.30 ± 4.30 (PLD) and 7.96 ± 0.72 (PHD) μg mL⁻¹ and dexmedetomidine concentrations were 0.68 ± 0.12 (PLD) and 0.89 ± 0.08 (PHD) ng mL⁻¹ at MIR_NM determination.
Dexmedetomidine (1 and 2 μg kg⁻¹) decreased propofol induction dose. Dexmedetomidine (2 μg kg⁻¹ hour⁻¹) resulted in a significant decrease in propofol MIR_NM.
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2017, Veterinary Anaesthesia and Analgesia
To determine the effect of fentanyl on the induction dose of propofol and minimum infusion rate required to prevent movement in response to noxious stimulation (MIR_NM) in dogs.
Crossover experimental design.
Six healthy, adult intact male Beagle dogs, mean ± standard deviation 12.6 ± 0.4 kg.
Dogs were administered 0.9% saline (treatment P), fentanyl (5 μg kg⁻¹) (treatment PLDF) or fentanyl (10 μg kg⁻¹) (treatment PHDF) intravenously over 5 minutes. Five minutes later, anesthesia was induced with propofol (2 mg kg⁻¹, followed by 1 mg kg⁻¹ every 15 seconds to achieve intubation) and maintained for 90 minutes by constant rate infusions (CRIs) of propofol alone or with fentanyl: P, propofol (0.5 mg kg⁻¹ minute⁻¹); PLDF, propofol (0.35 mg kg⁻¹ minute⁻¹) and fentanyl (0.1 μg kg⁻¹ minute⁻¹); PHDF, propofol (0.3 mg kg⁻¹ minute⁻¹) and fentanyl (0.2 μg kg⁻¹ minute⁻¹). Propofol CRI was increased or decreased based on the response to stimulation (50 V, 50 Hz, 10 mA), with 20 minutes between adjustments. Data were analyzed using a mixed-model anova and presented as mean ± standard error.
ropofol induction doses were 6.16 ± 0.31, 3.67 ± 0.21 and 3.33 ± 0.42 mg kg⁻¹ for P, PLDF and PHDF, respectively. Doses for PLDF and PHDF were significantly decreased from P (p < 0.05) but not different between treatments. Propofol MIR_NM was 0.60 ± 0.04, 0.29 ± 0.02 and 0.22 ± 0.02 mg kg⁻¹ minute⁻¹ for P, PLDF and PHDF, respectively. MIR_NM in PLDF and PHDF was significantly decreased from P. MIR_NM in PLDF and PHDF were not different, but their respective percent decreases of 51 ± 3 and 63 ± 2% differed (p = 0.035).
Fentanyl, at the doses studied, caused statistically significant and clinically important decreases in the propofol induction dose and MIR_NM.

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Short CommunicationThe incidence of spontaneous movements (myoclonus) in dogs undergoing total intravenous anaesthesia with propofol

Abstract

Objective

Study design

Animals

Methods

Results

Conclusions and clinical relevance

Introduction

Section snippets

Materials and methods

Results

Discussion

J Vet Anaesth

Clin Neurophysiol

Lidocaine pretreatment for the prevention of propofol-induced transient motor disturbances in children during anesthesia induction: a randomized controlled trial in children undergoing invasive hematologic procedures

Pediatr Anesth

Propofol and spontaneous movements: an electroencephalographic study

Anesthesiology

A clinical trial of propofol infusion anaesthesia in dogs

J Small Anim Pract

Short Communication
The incidence of spontaneous movements (myoclonus) in dogs undergoing total intravenous anaesthesia with propofol