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Paper
Paper Continuous infusion of remifentanil combined with target-controlled infusion of propofol for tracheal intubation in dogs Z. Pei, Y. Mao, S. Wang, X. Tang Ninety dogs presenting for elective surgery were randomly assigned into three groups of 30. Intubation conditions, haemodynamic responses and other events were evaluated following target controlled infusion (TCI) with propofol at 3.0 µg/ml, combined with variable infusion rates of remifentanil (R1 0.1 µg/kg/minute, R2 0.2 µg/kg/minute, R3 0.3 µg/ kg/minute). Tracheal intubation was recorded as excellent, good or poor according to jaw relaxation, tongue withdrawal, ease of laryngoscopy, swallowing, coughing and limb movement. Excellent overall intubation conditions were present in 5/30 (17 per cent), 12/30 (40 per cent) and 21/30 (70 per cent) of dogs in groups R1–3, respectively. In all three groups, the mean arterial pressure (MAP) and mean heart rate (MHR) decreased following induction of anaesthesia. Following intubation, despite an increase in MAP and MHR values, they remained significantly lower than baseline values. Muscle twitching and involuntary movement was observed after propofol induction in 10 dogs. The results suggest that a plasma concentration of 3 µg/ml propofol along with an infusion rate of remifentanil at 0.3 µg/kg/minute may provide satisfactory conditions for intubation, while avoiding major adverse haemodynamic effects.
Introduction
Increasingly, total intravenous anaesthesia (TIVA) is used as a practical technique with high potential in both human and veterinary anaesthesiology. In comparison with multiple boluses, TIVA with a continuous rate of infusion provides more stable drug concentrations, resulting in a better quality of anaesthesia with less haemodynamic instability (Gepts 1998). Target-controlled infusion (TCI) delivers a calculated drug quantity with a rapid infusion rate until the desired target concentration is achieved and thereafter maintains this concentration accurately. TCI provides the closest approximation of the drug concentration in the blood for any individual patient (Beths and others 2001, Musk and others 2005). For both the induction and maintenance of anaesthesia, propofol, widely used in human anaesthesia and increasingly popular in veterinary medicine (Joubert and others 2004, Musk and Flaherty 2007, Gimenes and others 2011), seems to be the optimal hypnotic agent for TIVA (Morgan and Legge 1989, Nolan and Reid 1993, Musk and others 2005). The well-reported pharmacokinetics of propofol Veterinary Record (2014) Z. Pei, S. Wang, Department of Veterinary Medicine (Small Animal Section), College of Animal Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, PR China Y. Mao, X. Tang, Department of Veterinary Medicine (Small Animal Section), Veterinary
doi: 10.1136/vr.101995 Teaching Hospital, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, PR China; Correspondence to Dr Zengyang Pei, e-mail: [email protected] Provenance: Not commissioned; externally peer reviewed Accepted April 2, 2014
(Mandsager and others 1995, Reid and Nolan 1996, Mertens and others 2003, Murrell and others 2005), show its advantage as the most suitable drug for the maintenance of anaesthesia by TIVA with continuous rate infusion. However, with its minimal analgesic effect it is often administered together with an opioid (Aguiar and others 2001, Fassoulaki 2011). Remifentanil is an ultrashort acting u-receptor agonist opioid, the pharmacokinetics of which are well documented for use in both humans and dogs (Hoffman and others 1993, Egan 1995, Egan and others 1996, Kabbaj and others 2005). Its pharmacological profile makes remifentanil appropriate as part of a total intravenous anaesthesia technique for elective surgery. In human studies, remifentanil gives intense analgesia with a rapid onset and ultrashort duration of action. This makes it optimal for attenuating multiple bouts of brief but strongly noxious stimuli, such as in cases of tracheal intubation or surgical incision (Hall and others 2000, Lee and others 2001). Many potential benefits of the combination of remifentanil and propofol in providing adequate conditions for induction of anaesthesia have been described in humans (Lee and others 2001, Park and others 2007, Polaner and others 2010). In particular, Michelsen and others (1996) demonstrated that remifentanil reduces anaesthetic requirements in humans. Both Mertens and others (2003) and Milne and others (2003) report a dose-dependent decrease in propofol requirement with increasing remifentanil plasma concentration in human patients. It is anticipated that remifentanil may have similar pharmacodynamic interactions with propofol in dogs. The simultaneous infusion of propofol and remifentanil for the induction and maintenance of anaesthesia in dogs has been described by Murrell and others (2005) and Musk and Flaherty (2007). In the latter study, the propofol/ remifentanil combination in TIVA was concluded to be easy to perform, provide satisfactory intraoperative conditions, smooth, rapid recovery and was devoid of severe adverse cardiovascular side effects. August 2, 2014 | Veterinary Record
Downloaded from veterinaryrecord.bmj.com on October 13, 2014 - Published by group.bmj.com
Paper For TIVA in dogs, Murrell and others (2005) concluded that remifentanil may be more suitable for use in combination with propofol than with other short-acting opioids. Remifentanil’s pharmacodynamic interactions with propofol in reducing anaesthetic requirements (see Michelsen and others 1996) and the potential for a low-dose constant rate infusion of remifentanil to provide greater haemodynamic stability and faster biotransformation (Gimenes and others 2011) are therefore of significant interest for veterinary anaesthesiology. For dosage in dogs, in a 16-dog study, Beths and others (2001) concluded that a blood target propofol concentration of 3.0 µg/ml provided for a remarkably smooth and controlled anaesthesia sufficient for tracheal intubation within three minutes. Musk and others (2005) then compared four different propofol target concentrations in the anaesthesia of healthy dogs, premedicated with acepromazine and morphine, using TCI and suggested an optimal target of 3.5 µg/ml propofol. For the propofol/remifentanil combination, Musk and Flaherty (2007) suggested that a target of 3.0–3.5 µg/ml propofol in plasma, in conjunction with remifentanil administered at 0.2–0.6 µg/ kg/minute, provided adequate reflex suppression during surgery. However, this latter study did not investigate the optimal remifentanil infusion rates for this propofol/remifentanil combination.
Materials and methods
To more accurately clarify the optimal infusion rate of remifentanil required for the steady induction and successful tracheal intubation in dogs during TCI with propofol, the authors chose a target of 3.0 µg/ml propofol in blood with infusion rates of 0.1, 0.2 or 0.3 µg/kg/minute remifentanil. As for propofol, the half-life for equilibration between blood and the drug’s action site is considered as approximately 2.6 minutes (Iwakiri and others 2005, Musk and others 2005), intubation, in this study, was at three minutes following induction. This study had approval from the Ethics Committee of Zhejiang University and was conducted with informed written consent from the owners of the 96 client-owned dogs. The dogs, aged between 11 months and 8 years, had American Society of Anesthesiologists (ASA) physical scores of either 1 or 2. They had been presented for minor to moderate surgical procedures at the veterinary teaching hospital of Zhejiang University and were studied in a randomised, blind trial. Dogs that had been previously anaesthetised within the past three weeks were excluded from the study. After a preanaesthetic clinical examination, the dogs were allocated, by random number selection, to one of three groups. Food was withheld for at least eight hours prior to anaesthesia, but water was freely available. The dogs were premedicated with a mix of 0.05 mg/kg atropine sulfate and 0.1 mg/kg acepromazine maleate by intravenous injection (Anamav injection; Mavlab), and 4 mg/kg tolfenamic acid (Tolfedine CS injection; Vetoquinol SA) by intramuscular injection, 30 minutes before induction of anaesthesia. Each dog was then placed in right lateral recumbency. All dogs were preoxygenated using 100 per cent oxygen via a face mask before and during the induction of anaesthesia. A venous catheter (Introcan; Braun) was placed in one cephalic vein for anaesthetic delivery. The other cephalic vein was catheterised for fluid administration during the intubation and maintenance period, using 10 ml/kg/hour lactated Ringer’s solution. Anaesthesia was induced with a combination of remifentanil (Ruijie; Yichang Humanwell) and propofol (Diprivan; AstraZeneca S.P.A). Remifentanil was delivered intravenously for five minutes at three different rates to the three groups: R1 (0.1 µg/kg/minute), R2 (0.2 µg/kg/minute) and R3 (0.3 µg/kg/minute), while preoxygenation continued. The doses of remifentanil were chosen on the basis of preliminary pilot studies. After a five-minute infusion of remifentanil, utilising a triple lumen administration set (three-way multiple infusion set; Kyoling), propofol was then intravenously infused, concurrent to continued remifentanil infusion, using a Target-control Infusion System programmed for propofol in dogs (Graseby 3500; Sims Graseby). The age and weight of the dog were entered as variable parameters, and the target blood concentration was selected at 3.0 µg/ml based on previous findings (Beths and others 2001, Musk and others 2005). Three minutes after propofol TCI infusion, endotracheal intubation was attempted with the aid of a laryngoscope by an experienced Veterinary Record | August 2, 2014
anaesthetist using an appropriately sized cuffed tracheal tube where the cuff was inflated slowly over the following three seconds. The anaesthetist who performed or evaluated the condition of intubation was unaware of the dose of remifentanil used. Dogs whose tracheas were not intubated at the first attempt were given further propofol, at the discretion of the then unblinded anaesthetist, prior to a second intubation attempt. No further data were recorded from those dogs, and a maximum time of 30 seconds was allowed per intubation attempt. After tracheal intubation, the dogs were connected to a mechanical ventilation system (CDS9000; Smiths Medical) with 100 per cent oxygen delivered to maintain the end-tidal partial pressure of carbon dioxide (PE’CO2) between 35 and 45 mm Hg. The ventilator settings were adjusted to achieve a respiratory rate of 10 breaths per minute, a relative inspiration/expiration (I:E) of 1:2, with the tidal volume of the bellows set to 20 ml/kg. Anaesthesia was then maintained with propofol at 3.0 µg/ml, and with remifentanil at one of the three different dose rates. No further stimulation was applied to the dog during the study period. The heart rate (HR) of each dog, together with its respiratory rate and mean arterial pressure (MAP), was obtained before induction of anaesthesia (time 1), and then after five minutes of remifentanil infusion (time 2), after propofol induction (time 3) and immediately after the dog had been intubated (time 4). Further measurements were obtained every one minute after intubation for five minutes (times 5–9). Peripheral oxygen saturation (SPO2) and end-tidal carbon dioxide (PE’CO2) were also monitored (V9212AR; Smiths Medical). Rectal temperature was measured using a digital thermometer and maintained between 37.5 and 38.5°C with an electric heating pad. The baseline HR was measured by cardiac auscultation and the subsequent HRs were obtained by palpation of a peripheral pulse and confirmation by electrocardiogram (CardEX 300; Midmark). The respiratory rate was recorded by observing the movements of the thoracic wall and confirmed by the breathing system. Arterial blood pressure was recorded oscillometrically (V9212AR; Smiths Medical) with an appropriately sized cuff placed over the dorsal pedal artery. A single measurement was taken at each time point. If the MAP decreased below 60 mm Hg for a second consecutive measurement or below 50 mm Hg at any point measurement, ephedrine was to be administered. If the HR decreased below 60 beats per minute for longer than 60 seconds, atropine was to be administered. After collection of the final data, five minutes after intubation, the anaesthetic was continued or adjusted according to requirements for the individual case. As shown in Table 1, the quality of tracheal intubation was assessed using a modified version of the widely used human intubation scoring system (Steyn and others 1994). Despite being formulated for use in humans, this system measures at least six factors (jaw relaxation, tongue withdrawal, ease of laryngoscopy, swallowing, coughing and limb movement) that are broadly applicable to both dog and human subjects. All factors were allocated a score of 1–3, and overall intubation conditions were recorded as ‘excellent’ if all scored 1, ‘good’ if any scored 2 and ‘poor’ if there were any scores of 3. Intubation conditions were judged acceptable when all scores were 2 or less and unacceptable if any of the scores were 3. Adverse events such as laryngospasm, severe hypotension or muscle rigidity, and the administration of further drugs were also recorded. Results are presented as mean±sd unless stated otherwise. Statistical analysis was performed to investigate differences from basal values in each treatment using repeated measures analysis of variance TABLE 1: Scoring criteria for conditions of intubation (modified human intubation scoring system) Score
1
2
3
Jaw relaxation Tongue withdrawal Laryngoscopy Swallowing Coughing
Relaxed None
Not fully Slight
Rigid Severe
Easy None None
Limb movement
None
Fair Slight One or two coughs Slight
Difficult Severe Persistent coughing Severe
Downloaded from veterinaryrecord.bmj.com on October 13, 2014 - Published by group.bmj.com
Paper
A total of 96 dogs were enrolled into the study. Six dogs, however, were withdrawn once recruited: two dogs received a gaseous induction due to failed intravenous access; and four dogs had incomplete data collection. Any data from these six was excluded. Of the 90 dogs who completed the study, there were an equal number in each group. All were aged between 11 months and 8 years and between 2.7 and 35.6 kg in weight. Thirteen different breeds were represented, with miniature poodle being the most common (n=45), followed by Pekingese (n=23). There were no significant differences in patient demographics between the three groups (data not shown). The scores for each condition are shown in Table 2. All dogs from the R3 group were successfully intubated on the first attempt. However, seven dogs in R1 and two dogs in R2 could not be intubated because of poor jaw relaxation or severe tongue withdrawal. Intubation was completed in these nine dogs following higher target concentrations of propofol infusion. The overall assessment of intubation conditions was acceptable in 14/30 (47 per cent) dogs in group R1, in 24/30 (80 per cent) dogs in R2 and in 29/30 (97 per cent) dogs in R3. Overall, groups R2 and R3 achieved better intubation conditions than did R1. Excellent overall intubation conditions were present in 5/30 (17 per cent) dogs in the R1 group, followed by 12/30 (40 per cent) and 21/30 (70 per cent) for dogs in R2 and R3, respectively. In R1, of the nine dogs with unacceptable intubation conditions, two had jaw stiffness, two had severe limb movement and five had sustained coughing. Four dogs in R2 and one dog in R3 were also deemed to have unacceptable intubation conditions. In R2, three displayed severe limb movements and one of each group exhibited sustained coughing. The haemodynamic changes within each group are summarised in Figs 1 and 2. There were no significant differences in haemodynamic variables between groups prior to induction. For all three groups, the mean heart rate (MHR) decreased significantly after remifentanil infusion (time 2). In groups R2 and R3, the MHR significantly decreased again after propofol induction (time 3), but this was not the case for group R1 (P=0.974 compared with time 2). Following laryngoscopy and tracheal intubation, despite increasing, the MHR values remained significantly lower than baseline values (time 1) for all groups. There was a slight but insignificant increase in MHR in the R1 group from time 3 to times 4, 5 and 6. In R2, there was a significant drop in MHR from time 3 to time 4 (P=0.037), followed by a significant increasing trend when comparing time 4 to each of the subsequent times up to and including time 7. In R3, there were no significant changes in MHR after intubation and an insignificant decreasing trend when comparing time 3 with times 4–8. In R3, the greatest decrease in MHR was recorded five minutes after intubation (time 9), which was significantly different from that of time 3 (P=0.001). The MAPs after remifentanil infusion (time 2) were significantly decreased in all three groups compared with baseline values (time 1). Similarly, further significant decreases in MAP were recorded immediately after propofol induction (time 3) in all three groups as compared with times 1 or 2. The MAP in R2 and R3 did not increase TABLE 2: Intubation conditions Acceptable Acceptable Unacceptable Failed at first attempt
Excellent Good Poor
R1 (n=30)
R2 (n=30)
R3 (n=30)
5 9 9 7
12 12 4 2
21 8 1 0
R1 R2 R3
130 MHR (Beat/min)
Results
140
120
110 100
#
#
90 80 1
2
3
4
5 6 Time points
7
8
9
FIG 1: Change in MHR during the study in all groups (Mean ± SD). Time 1, before induction; time 2, immediately after remifentanil infusion; time 3, after propofol induction; time 4, immediately after intubation; time 5-9, every further 1 min after intubation for 5 min. *p
Paper
Paper Continuous infusion of remifentanil combined with target-controlled infusion of propofol for tracheal intubation in dogs Z. Pei, Y. Mao, S. Wang, X. Tang Ninety dogs presenting for elective surgery were randomly assigned into three groups of 30. Intubation conditions, haemodynamic responses and other events were evaluated following target controlled infusion (TCI) with propofol at 3.0 µg/ml, combined with variable infusion rates of remifentanil (R1 0.1 µg/kg/minute, R2 0.2 µg/kg/minute, R3 0.3 µg/ kg/minute). Tracheal intubation was recorded as excellent, good or poor according to jaw relaxation, tongue withdrawal, ease of laryngoscopy, swallowing, coughing and limb movement. Excellent overall intubation conditions were present in 5/30 (17 per cent), 12/30 (40 per cent) and 21/30 (70 per cent) of dogs in groups R1–3, respectively. In all three groups, the mean arterial pressure (MAP) and mean heart rate (MHR) decreased following induction of anaesthesia. Following intubation, despite an increase in MAP and MHR values, they remained significantly lower than baseline values. Muscle twitching and involuntary movement was observed after propofol induction in 10 dogs. The results suggest that a plasma concentration of 3 µg/ml propofol along with an infusion rate of remifentanil at 0.3 µg/kg/minute may provide satisfactory conditions for intubation, while avoiding major adverse haemodynamic effects.
Introduction
Increasingly, total intravenous anaesthesia (TIVA) is used as a practical technique with high potential in both human and veterinary anaesthesiology. In comparison with multiple boluses, TIVA with a continuous rate of infusion provides more stable drug concentrations, resulting in a better quality of anaesthesia with less haemodynamic instability (Gepts 1998). Target-controlled infusion (TCI) delivers a calculated drug quantity with a rapid infusion rate until the desired target concentration is achieved and thereafter maintains this concentration accurately. TCI provides the closest approximation of the drug concentration in the blood for any individual patient (Beths and others 2001, Musk and others 2005). For both the induction and maintenance of anaesthesia, propofol, widely used in human anaesthesia and increasingly popular in veterinary medicine (Joubert and others 2004, Musk and Flaherty 2007, Gimenes and others 2011), seems to be the optimal hypnotic agent for TIVA (Morgan and Legge 1989, Nolan and Reid 1993, Musk and others 2005). The well-reported pharmacokinetics of propofol Veterinary Record (2014) Z. Pei, S. Wang, Department of Veterinary Medicine (Small Animal Section), College of Animal Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, PR China Y. Mao, X. Tang, Department of Veterinary Medicine (Small Animal Section), Veterinary
doi: 10.1136/vr.101995 Teaching Hospital, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, PR China; Correspondence to Dr Zengyang Pei, e-mail: [email protected] Provenance: Not commissioned; externally peer reviewed Accepted April 2, 2014
(Mandsager and others 1995, Reid and Nolan 1996, Mertens and others 2003, Murrell and others 2005), show its advantage as the most suitable drug for the maintenance of anaesthesia by TIVA with continuous rate infusion. However, with its minimal analgesic effect it is often administered together with an opioid (Aguiar and others 2001, Fassoulaki 2011). Remifentanil is an ultrashort acting u-receptor agonist opioid, the pharmacokinetics of which are well documented for use in both humans and dogs (Hoffman and others 1993, Egan 1995, Egan and others 1996, Kabbaj and others 2005). Its pharmacological profile makes remifentanil appropriate as part of a total intravenous anaesthesia technique for elective surgery. In human studies, remifentanil gives intense analgesia with a rapid onset and ultrashort duration of action. This makes it optimal for attenuating multiple bouts of brief but strongly noxious stimuli, such as in cases of tracheal intubation or surgical incision (Hall and others 2000, Lee and others 2001). Many potential benefits of the combination of remifentanil and propofol in providing adequate conditions for induction of anaesthesia have been described in humans (Lee and others 2001, Park and others 2007, Polaner and others 2010). In particular, Michelsen and others (1996) demonstrated that remifentanil reduces anaesthetic requirements in humans. Both Mertens and others (2003) and Milne and others (2003) report a dose-dependent decrease in propofol requirement with increasing remifentanil plasma concentration in human patients. It is anticipated that remifentanil may have similar pharmacodynamic interactions with propofol in dogs. The simultaneous infusion of propofol and remifentanil for the induction and maintenance of anaesthesia in dogs has been described by Murrell and others (2005) and Musk and Flaherty (2007). In the latter study, the propofol/ remifentanil combination in TIVA was concluded to be easy to perform, provide satisfactory intraoperative conditions, smooth, rapid recovery and was devoid of severe adverse cardiovascular side effects. August 2, 2014 | Veterinary Record
Downloaded from veterinaryrecord.bmj.com on October 13, 2014 - Published by group.bmj.com
Paper For TIVA in dogs, Murrell and others (2005) concluded that remifentanil may be more suitable for use in combination with propofol than with other short-acting opioids. Remifentanil’s pharmacodynamic interactions with propofol in reducing anaesthetic requirements (see Michelsen and others 1996) and the potential for a low-dose constant rate infusion of remifentanil to provide greater haemodynamic stability and faster biotransformation (Gimenes and others 2011) are therefore of significant interest for veterinary anaesthesiology. For dosage in dogs, in a 16-dog study, Beths and others (2001) concluded that a blood target propofol concentration of 3.0 µg/ml provided for a remarkably smooth and controlled anaesthesia sufficient for tracheal intubation within three minutes. Musk and others (2005) then compared four different propofol target concentrations in the anaesthesia of healthy dogs, premedicated with acepromazine and morphine, using TCI and suggested an optimal target of 3.5 µg/ml propofol. For the propofol/remifentanil combination, Musk and Flaherty (2007) suggested that a target of 3.0–3.5 µg/ml propofol in plasma, in conjunction with remifentanil administered at 0.2–0.6 µg/ kg/minute, provided adequate reflex suppression during surgery. However, this latter study did not investigate the optimal remifentanil infusion rates for this propofol/remifentanil combination.
Materials and methods
To more accurately clarify the optimal infusion rate of remifentanil required for the steady induction and successful tracheal intubation in dogs during TCI with propofol, the authors chose a target of 3.0 µg/ml propofol in blood with infusion rates of 0.1, 0.2 or 0.3 µg/kg/minute remifentanil. As for propofol, the half-life for equilibration between blood and the drug’s action site is considered as approximately 2.6 minutes (Iwakiri and others 2005, Musk and others 2005), intubation, in this study, was at three minutes following induction. This study had approval from the Ethics Committee of Zhejiang University and was conducted with informed written consent from the owners of the 96 client-owned dogs. The dogs, aged between 11 months and 8 years, had American Society of Anesthesiologists (ASA) physical scores of either 1 or 2. They had been presented for minor to moderate surgical procedures at the veterinary teaching hospital of Zhejiang University and were studied in a randomised, blind trial. Dogs that had been previously anaesthetised within the past three weeks were excluded from the study. After a preanaesthetic clinical examination, the dogs were allocated, by random number selection, to one of three groups. Food was withheld for at least eight hours prior to anaesthesia, but water was freely available. The dogs were premedicated with a mix of 0.05 mg/kg atropine sulfate and 0.1 mg/kg acepromazine maleate by intravenous injection (Anamav injection; Mavlab), and 4 mg/kg tolfenamic acid (Tolfedine CS injection; Vetoquinol SA) by intramuscular injection, 30 minutes before induction of anaesthesia. Each dog was then placed in right lateral recumbency. All dogs were preoxygenated using 100 per cent oxygen via a face mask before and during the induction of anaesthesia. A venous catheter (Introcan; Braun) was placed in one cephalic vein for anaesthetic delivery. The other cephalic vein was catheterised for fluid administration during the intubation and maintenance period, using 10 ml/kg/hour lactated Ringer’s solution. Anaesthesia was induced with a combination of remifentanil (Ruijie; Yichang Humanwell) and propofol (Diprivan; AstraZeneca S.P.A). Remifentanil was delivered intravenously for five minutes at three different rates to the three groups: R1 (0.1 µg/kg/minute), R2 (0.2 µg/kg/minute) and R3 (0.3 µg/kg/minute), while preoxygenation continued. The doses of remifentanil were chosen on the basis of preliminary pilot studies. After a five-minute infusion of remifentanil, utilising a triple lumen administration set (three-way multiple infusion set; Kyoling), propofol was then intravenously infused, concurrent to continued remifentanil infusion, using a Target-control Infusion System programmed for propofol in dogs (Graseby 3500; Sims Graseby). The age and weight of the dog were entered as variable parameters, and the target blood concentration was selected at 3.0 µg/ml based on previous findings (Beths and others 2001, Musk and others 2005). Three minutes after propofol TCI infusion, endotracheal intubation was attempted with the aid of a laryngoscope by an experienced Veterinary Record | August 2, 2014
anaesthetist using an appropriately sized cuffed tracheal tube where the cuff was inflated slowly over the following three seconds. The anaesthetist who performed or evaluated the condition of intubation was unaware of the dose of remifentanil used. Dogs whose tracheas were not intubated at the first attempt were given further propofol, at the discretion of the then unblinded anaesthetist, prior to a second intubation attempt. No further data were recorded from those dogs, and a maximum time of 30 seconds was allowed per intubation attempt. After tracheal intubation, the dogs were connected to a mechanical ventilation system (CDS9000; Smiths Medical) with 100 per cent oxygen delivered to maintain the end-tidal partial pressure of carbon dioxide (PE’CO2) between 35 and 45 mm Hg. The ventilator settings were adjusted to achieve a respiratory rate of 10 breaths per minute, a relative inspiration/expiration (I:E) of 1:2, with the tidal volume of the bellows set to 20 ml/kg. Anaesthesia was then maintained with propofol at 3.0 µg/ml, and with remifentanil at one of the three different dose rates. No further stimulation was applied to the dog during the study period. The heart rate (HR) of each dog, together with its respiratory rate and mean arterial pressure (MAP), was obtained before induction of anaesthesia (time 1), and then after five minutes of remifentanil infusion (time 2), after propofol induction (time 3) and immediately after the dog had been intubated (time 4). Further measurements were obtained every one minute after intubation for five minutes (times 5–9). Peripheral oxygen saturation (SPO2) and end-tidal carbon dioxide (PE’CO2) were also monitored (V9212AR; Smiths Medical). Rectal temperature was measured using a digital thermometer and maintained between 37.5 and 38.5°C with an electric heating pad. The baseline HR was measured by cardiac auscultation and the subsequent HRs were obtained by palpation of a peripheral pulse and confirmation by electrocardiogram (CardEX 300; Midmark). The respiratory rate was recorded by observing the movements of the thoracic wall and confirmed by the breathing system. Arterial blood pressure was recorded oscillometrically (V9212AR; Smiths Medical) with an appropriately sized cuff placed over the dorsal pedal artery. A single measurement was taken at each time point. If the MAP decreased below 60 mm Hg for a second consecutive measurement or below 50 mm Hg at any point measurement, ephedrine was to be administered. If the HR decreased below 60 beats per minute for longer than 60 seconds, atropine was to be administered. After collection of the final data, five minutes after intubation, the anaesthetic was continued or adjusted according to requirements for the individual case. As shown in Table 1, the quality of tracheal intubation was assessed using a modified version of the widely used human intubation scoring system (Steyn and others 1994). Despite being formulated for use in humans, this system measures at least six factors (jaw relaxation, tongue withdrawal, ease of laryngoscopy, swallowing, coughing and limb movement) that are broadly applicable to both dog and human subjects. All factors were allocated a score of 1–3, and overall intubation conditions were recorded as ‘excellent’ if all scored 1, ‘good’ if any scored 2 and ‘poor’ if there were any scores of 3. Intubation conditions were judged acceptable when all scores were 2 or less and unacceptable if any of the scores were 3. Adverse events such as laryngospasm, severe hypotension or muscle rigidity, and the administration of further drugs were also recorded. Results are presented as mean±sd unless stated otherwise. Statistical analysis was performed to investigate differences from basal values in each treatment using repeated measures analysis of variance TABLE 1: Scoring criteria for conditions of intubation (modified human intubation scoring system) Score
1
2
3
Jaw relaxation Tongue withdrawal Laryngoscopy Swallowing Coughing
Relaxed None
Not fully Slight
Rigid Severe
Easy None None
Limb movement
None
Fair Slight One or two coughs Slight
Difficult Severe Persistent coughing Severe
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Paper
A total of 96 dogs were enrolled into the study. Six dogs, however, were withdrawn once recruited: two dogs received a gaseous induction due to failed intravenous access; and four dogs had incomplete data collection. Any data from these six was excluded. Of the 90 dogs who completed the study, there were an equal number in each group. All were aged between 11 months and 8 years and between 2.7 and 35.6 kg in weight. Thirteen different breeds were represented, with miniature poodle being the most common (n=45), followed by Pekingese (n=23). There were no significant differences in patient demographics between the three groups (data not shown). The scores for each condition are shown in Table 2. All dogs from the R3 group were successfully intubated on the first attempt. However, seven dogs in R1 and two dogs in R2 could not be intubated because of poor jaw relaxation or severe tongue withdrawal. Intubation was completed in these nine dogs following higher target concentrations of propofol infusion. The overall assessment of intubation conditions was acceptable in 14/30 (47 per cent) dogs in group R1, in 24/30 (80 per cent) dogs in R2 and in 29/30 (97 per cent) dogs in R3. Overall, groups R2 and R3 achieved better intubation conditions than did R1. Excellent overall intubation conditions were present in 5/30 (17 per cent) dogs in the R1 group, followed by 12/30 (40 per cent) and 21/30 (70 per cent) for dogs in R2 and R3, respectively. In R1, of the nine dogs with unacceptable intubation conditions, two had jaw stiffness, two had severe limb movement and five had sustained coughing. Four dogs in R2 and one dog in R3 were also deemed to have unacceptable intubation conditions. In R2, three displayed severe limb movements and one of each group exhibited sustained coughing. The haemodynamic changes within each group are summarised in Figs 1 and 2. There were no significant differences in haemodynamic variables between groups prior to induction. For all three groups, the mean heart rate (MHR) decreased significantly after remifentanil infusion (time 2). In groups R2 and R3, the MHR significantly decreased again after propofol induction (time 3), but this was not the case for group R1 (P=0.974 compared with time 2). Following laryngoscopy and tracheal intubation, despite increasing, the MHR values remained significantly lower than baseline values (time 1) for all groups. There was a slight but insignificant increase in MHR in the R1 group from time 3 to times 4, 5 and 6. In R2, there was a significant drop in MHR from time 3 to time 4 (P=0.037), followed by a significant increasing trend when comparing time 4 to each of the subsequent times up to and including time 7. In R3, there were no significant changes in MHR after intubation and an insignificant decreasing trend when comparing time 3 with times 4–8. In R3, the greatest decrease in MHR was recorded five minutes after intubation (time 9), which was significantly different from that of time 3 (P=0.001). The MAPs after remifentanil infusion (time 2) were significantly decreased in all three groups compared with baseline values (time 1). Similarly, further significant decreases in MAP were recorded immediately after propofol induction (time 3) in all three groups as compared with times 1 or 2. The MAP in R2 and R3 did not increase TABLE 2: Intubation conditions Acceptable Acceptable Unacceptable Failed at first attempt
Excellent Good Poor
R1 (n=30)
R2 (n=30)
R3 (n=30)
5 9 9 7
12 12 4 2
21 8 1 0
R1 R2 R3
130 MHR (Beat/min)
Results
140
120
110 100
#
#
90 80 1
2
3
4
5 6 Time points
7
8
9
FIG 1: Change in MHR during the study in all groups (Mean ± SD). Time 1, before induction; time 2, immediately after remifentanil infusion; time 3, after propofol induction; time 4, immediately after intubation; time 5-9, every further 1 min after intubation for 5 min. *p
